bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of clinical features and prognostic factors in Takayasu arteritis involving pulmonary hypertension: A retrospective study
Authors: Wang Jinxia , Lei Kai , Li Jinxia , Zhang Yanan , Chi Shuhong , Zhang Zhengping , Huang Lingyan , Yang Xia
Published: May 2024

Background:

Multiple takayasu arteritis (TA) is a chronic nonspecific large to medium vasculitis disease that mainly accumulates the aorta and its branches. Pulmonary vascular disease is often seen as stenosis and occlusion, and patients may show no moderate to severe pulmonary hypertension (PH). This study aims to summarize the clinical characteristics and analysis of prognostic factors in patients with PH caused by TA.

Methods:

Patients diagnosed with aortitis involving the pulmonary artery by pulmonary arteriography or pulmonary artery and total aortic computed tomography arteriography (CTA). All patients underwent detailed clinical assessment, laboratory data collection, and analysis of imaging data. Patients were followed up and factors affecting the prognosis of the pulmonary arteries were analyzed.

Results:

Most of the patients’ complaints were chest tightness, shortness of breath, decreased activity tolerance, hemoptysis and chest pain. 56.90% of the patients were in at the time of admission. Echocardiographic estimation of pulmonary artery systolic pressure was 90.39 ± 22.87 mm Hg. In terms of laboratory tests, 39.66%% of the patients had elevated C-reactive protein and erythrocyte sedimentation rate, and amino-terminal natriuretic peptide precursor on admission. In terms of imaging, all patients had pulmonary artery involvement, which was combined with aortic involvement in 31.03%. Nuclide lung perfusion/ventilation imaging of the patients revealed multiple perfusion defects/absences in the segmental and subsegmental distribution of the lungs. Univariate Cox regression model analysis suggested that patients’ WHO functional class at admission, age ≧ 51 years at the time of consultation, and amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL were factors affecting the prognosis. Further multifactorial Cox regression model analysis suggested amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL was an independent predictor of poor prognosis with a hazard ratio (HR) value of 5.248.

Conclusion:

Electrocardiogram and echocardiogram may suggest an increased right heart load; some patients have elevated serum inflammatory indexes. Characteristic imaging manifestations include widening of the main pulmonary artery, multiple pulmonary segmental and subsegmental stenoses.
Development of mobile CAT for patient feedback on pediatric consultations based on Rasch analysis of online techniques
Authors: Hsieh Ju-Hao , Chow Julie Chi
Published: May 2024

The Rasch Rating Scale Model (RSM) is widely used in questionnaire analysis, providing insights into how individuals respond to item-level stimuli. Existing software for Rasch RSM parameter estimation, while powerful, often presents a steep learning curve. An accessible online tool can greatly benefit novice users, particularly students and clinicians, by simplifying the analytical process. This study introduces an online tool, an intuitive online RSM analysis tool designed to facilitate questionnaire data analysis for applied researchers, students, and clinicians. The online tool employs the joint maximum likelihood method for estimation, yielding estimates, standard errors (SE), and fit statistics iteratively. A unique feature of the tool is its ability to visualize estimates on Google Maps with an opacity setting of 0, enhancing data interpretation through a user-friendly interface. This study outlines the estimation process and key features, employing data from 200 proxy participants who answered 20 5-point questions regarding doctor-patient and doctor-family interactions in pediatric consultations. Mobile computerized adaptive testing (CAT) was employed. The online tool offers 5 essential visual displays often utilized in Rasch analyses, including the Wright Map, KIDMAP, category probability curve, performance plot, and differential item functioning (DIF) graph. DIF analysis revealed that 2 items, concerning the doctor attentiveness and empathy toward the child illness, exhibited differences in female proxy participants’ responses, indicating lower satisfaction with pediatricians. The online tool emerges as a user-friendly and efficient RSM analysis tool with notable advantages for newcomers, improving data visualization and comprehension. Its capacity to pinpoint key areas of concern, such as gender-related satisfaction disparities among proxy participants, enhances its utility in questionnaire analysis. The online tool holds promise as a valuable resource for researchers, students, and clinicians seeking accessible Rasch analysis solutions.
Comparative efficacy and safety of different drugs in patients with systemic juvenile idiopathic arthritis: A systematic review and network meta-analysis
Authors: Wang Baoquan , Zhang Yushan , Zhao Zhenbiao , Ping Juan , Zhou Liming , Wang Yining , Zhang Yongzhou
Published: May 2024

Background:

The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis.

Methods:

Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value.

Results:

We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4–67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously.

Conclusions:

Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.
Prevalence and risk of nonalcoholic fatty liver disease among adult psoriatic patients: A systematic review, meta-analysis, and trial sequential analysis
Authors: HU Jie , Shao YaQiong , Gui Cheng , Xiao Yihui , Li Lixia , Li Zheng
Published: May 2024

Background:

This systematic review and meta-analysis aimed to report the evaluation of the prevalence and risk of nonalcoholic fatty liver disease (NAFLD) among adult psoriatic patients in a systematic review and meta-analysis.

Methods:

A comprehensive search was conducted across 4 databases of PubMed, Scopus, Cochrane Library, and Web of Science to collect relevant studies until November 30, 2023, without any restrictions for finding observational studies. The comprehensive meta-analysis version 3.0 software was used to calculate effect sizes, showing the event rate (ER), odds ratio (OR), and a 95% confidence interval (CI) to evaluate NAFLD risk or prevalence in psoriatic patients and controls or psoriatic patients alone. The quality scoring was performed by 1 author based on the Newcastle-Ottawa Scale tool. Publication bias, meta-regression analysis, and sensitivity analyses were performed. Additionally, Trial Sequential Analysis (TSA) was performed using TSA software.

Results:

A total of 581 records were identified among the databases and electronic sources. At last, 41 studies involving 607,781 individuals were included in the meta-analysis. The pooled ER of NAFLD among psoriatic patients was 29.5% (95%CI: 19.6%–41.7%) and I
2 = 99.79%. The pooled OR of NAFLD in psoriatic patients compared to controls was 1.685 (95%CI: 1.382–2.055; P < .001) and I
2 = 87.96%.

Conclusions:

The study found a significant link between psoriasis and NAFLD, with psoriatic patients having a higher chance of developing NAFLD compared to the controls. The study calls for regular NAFLD screening in psoriatic patients to prevent liver complications.
Amoxicillin, gemifloxacin and rabeprazole, as first-line Helicobacter pylori therapy in clinical practice: A pilot study
Authors: Kilic Guner , Kilic Gulce Ecem , Özkahraman Adnan , Konur Sevki , Dertli Ramazan , Kayar Yusuf
Published: May 2024

Success in eradication of H. pylori is decreasing due to increasing resistant strains. In particular, side-effects due to 4-agent treatment multiple drug use are observed and treatment compliance decreases. The aim of this study was to evaluate the efficacy, reliability, and side-effect profile of the combination of amoxicillin and rabeprazole with gemifloxacin, which is a new generation quinolone, in the treatment of H. pylori infection. This study was conducted on 71 naive patients who received H. pylori eradication. All the patients were administered treatment of Amoxicillin (1000 mg twice a day) + Gemifloxacin (320 mg once a day) + rabeprazole (20 mg twice a day) for 7 days. Drug compliance and treatment tolerance were evaluated after finishing the treatment. At 1 month after the end of the treatment, H. pylori eradication was evaluated in all the patients by examining H. pylori antigen in the feces. In the evaluation after treatment, H. pylori eradication was obtained in 63 (88.7%) patients and eradication was not obtained in 8 (11.3%) patients. The treatment was not completed by 2 patients because of side-effects and noncompliance, so after exclusion of these 2 patients, successful H. pylori eradication was obtained in 63 (91.3%) of 69 patients who completed the treatment. Side-effects were seen in a total of 9 (12.7%) patients. Diarrhea, bloating, abdominal pain, and nausea-vomiting were seen in some patients, but no reflux, constipation, skin rash, listlessness-fatigue, headache, dizziness, palpitations, dry mouth, or weight loss was seen in any patient. In regions with high resistance to clarithromycin and metronidazole in particular, the combination of gemifloxacin with amoxicillin and rabeprazole can be considered for use in first-stage treatment as both the efficacy and tolerability are high.
Assessing the relative effectiveness of various ultrasound-guided ablation techniques for treating benign thyroid nodules: A systematic review and network meta-analysis
Authors: Sun Xiangmei , Chen Jiaojiao , Zou Yan , Lei Jiahao , Liu Weizong
Published: May 2024

Background:

Benign thyroid nodules (BTNs) represent a prevalent clinical challenge globally, with various ultrasound-guided ablation techniques developed for their management. Despite the availability of these methods, a comprehensive evaluation to identify the most effective technique remains absent. This study endeavors to bridge this knowledge gap through a network meta-analysis (NMA), aiming to enhance the understanding of the comparative effectiveness of different ultrasound-guided ablation methods in treating BTNs.

Methods:

We comprehensively searched PubMed, Embase, Cochrane, Web of Science, Ovid, SCOPUS, and ProQuest for studies involving 16 ablation methods, control groups, and head-to-head trials. NMA was utilized to evaluate methods based on the percentage change in nodule volume, symptom score, and cosmetic score. This study is registered in INPLASY (registration number 202260061).

Results:

Among 35 eligible studies involving 5655 patients, NMA indicated that RFA2 (radiofrequency ablation, 2 sessions) exhibited the best outcomes at 6 months for percentage change in BTN volume (SUCRA value 74.6), closely followed by RFA (SUCRA value 73.7). At 12 months, RFA was identified as the most effective (SUCRA value 81.3). Subgroup analysis showed RFA2 as the most effective for solid nodule volume reduction at 6 months (SUCRA value 75.6), and polidocanol ablation for cystic nodules (SUCRA value 66.5).

Conclusion:

Various ablation methods are effective in treating BTNs, with RFA showing notable advantages. RFA with 2 sessions is particularly optimal for solid BTNs, while polidocanol ablation stands out for cystic nodules.
Decoding the molecular landscape: A novel prognostic signature for uveal melanoma unveiled through programmed cell death-associated genes
Authors: Liu Zibin , Yu Lili , Lai Jian , Zhang Rui
Published: May 2024

Uveal melanoma (UM) is a rare but aggressive malignant ocular tumor with a high metastatic potential and limited therapeutic options, currently lacking accurate prognostic predictors and effective individualized treatment strategies. Public databases were utilized to analyze the prognostic relevance of programmed cell death-related genes (PCDRGs) in UM transcriptomes and survival data. Consensus clustering and Lasso Cox regression analysis were performed for molecular subtyping and risk feature construction. The PCDRG-derived index (PCDI) was evaluated for its association with clinicopathological features, gene expression, drug sensitivity, and immune infiltration. A total of 369 prognostic PCDRGs were identified, which could cluster UM into 2 molecular subtypes with significant differences in prognosis and clinicopathological characteristics. Furthermore, a risk feature PCDI composed of 11 PCDRGs was constructed, capable of indicating prognosis in UM patients. Additionally, PCDI exhibited correlations with the sensitivity to 25 drugs and the infiltration of various immune cells. Enrichment analysis revealed that PCDI was associated with immune regulation-related biological processes and pathways. Finally, a nomogram for prognostic assessment of UM patients was developed based on PCDI and gender, demonstrating excellent performance. This study elucidated the potential value of PCDRGs in prognostic assessment for UM and developed a corresponding risk feature. However, further basic and clinical studies are warranted to validate the functions and mechanisms of PCDRGs in UM.
Status and perception of point-of-care ultrasound education in Korean medical schools: A national cross-sectional study
Authors: Yoo Jonghoon , Kang Soo Yeon , Joon Jo Ik , Kim Taerim , Lee Gun Tak , Park Jong Eun , Lee Se Uk , Hwang Sung Yeon , Cha Won Chul , Shin Tae Gun , Cho Young Soon , Jang Hyewon , Yoon Hee
Published: May 2024

As point-of-care ultrasound (POCUS) is increasingly being used in clinical settings, ultrasound education is expanding into student curricula. We aimed to determine the status and awareness of POCUS education in Korean medical schools using a nationwide cross-sectional survey. In October 2021, a survey questionnaire consisting of 20 questions was distributed via e-mail to professors in the emergency medicine (EM) departments of Korean medical schools. The questionnaire encompassed 19 multiple-choice questions covering demographics, current education, perceptions, and barriers, and the final question was an open-ended inquiry seeking suggestions for POCUS education. All EM departments of the 40 medical schools responded, of which only 13 (33%) reported providing POCUS education. The implementation of POCUS education primarily occurred in the third and fourth years, with less than 4 hours of dedicated training time. Five schools offered a hands-on education. Among schools offering ultrasound education, POCUS training for trauma cases is the most common. Eight schools had designated professors responsible for POCUS education and only 2 possessed educational ultrasound devices. Of the respondents, 64% expressed the belief that POCUS education for medical students is necessary, whereas 36%, including those with neutral opinions, did not anticipate its importance. The identified barriers to POCUS education included faculty shortages (83%), infrastructure limitations (76%), training time constraints (74%), and a limited awareness of POCUS (29%). POCUS education in Korean medical schools was limited to a minority of EM departments (33%). To successfully implement POCUS education in medical curricula, it is crucial to clarify learning objectives, enhance faculty recognition, and improve the infrastructure. These findings provide valuable insights for advancing ultrasound training in medical schools to ensure the provision of high-quality POCUS education for future healthcare professionals.
β-Thalassemia gene editing therapy: Advancements and difficulties
Authors: Hu Jing , Zhong Yebing , Xu Pengxiang , Xin Liuyan , Zhu Xiaodan , Jiang Xinghui , Gao Weifang , Yang Bin , Chen Yijian
Published: May 2024

β-Thalassemia is the world’s number 1 single-gene genetic disorder and is characterized by suppressed or impaired production of β-pearl protein chains. This results in intramedullary destruction and premature lysis of red blood cells in peripheral blood. Among them, patients with transfusion-dependent β-thalassemia face the problem of long-term transfusion and iron chelation therapy, which leads to clinical complications and great economic stress. As gene editing technology improves, we are seeing the dawn of a cure for the disease, with its reduction of ineffective erythropoiesis and effective prolongation of survival in critically ill patients. Here, we provide an overview of β-thalassemia distribution and pathophysiology. In addition, we focus on gene therapy and gene editing advances. Nucleic acid endonuclease tools currently available for gene editing fall into 3 categories: zinc finger nucleases, transcription activator-like effector nucleases, and regularly interspaced short palindromic repeats (CRISPR-Cas9) nucleases. This paper reviews the exploratory applications and exploration of emerging therapeutic tools based on 3 classes of nucleic acid endonucleases in the treatment of β-thalassemia diseases.
Ultrasound-guided subcostal approach of transversus abdominis plane block compared with wound infiltration for postoperative analgesia following laparoscopic cholecystectomy: A systematic review and meta-analysis
Authors: Park Sukhee , Park Ji-Hoon , Park Soyoon , Jang Jae Ni , Kim Chaeeun , Choi Young-Soon
Published: May 2024

Background:

Despite laparoscopic cholecystectomy (LC) is a commonly performed operation under ambulatory setting, significant postoperative pain is still a major concern. The ultrasound-guided subcostal approach of transversus abdominis plane (sTAP) blocks and wound infiltration (WI) are both widely practiced techniques to reduce postoperative pain in patients undergoing LC. Although these methods have been shown to relieve postoperative pain effectively, the relative analgesic efficacy between ultrasound-guided sTAP blocks and WI is not well known.

Methods:

We searched PubMed, EMBASE, and CENTRAL to identify all randomized controlled trials (RCTs) comparing ultrasound-guided sTAP block versus WI for postoperative pain control in adult patients undergone LC. The search was performed until May 2023. Primary outcome was defined as 24-hour cumulative opioid consumption. Secondary outcomes were postoperative pain scores and the incidence of postoperative nausea and vomiting (PONV).

Results:

Finally, 6 RCTs were included, and data from 314 participants were retrieved. Postoperative 24-hour opioid consumption was significantly lower in ultrasound-guided sTAP group than in the WI group with a mean difference of −6.67 (95% confidence interval: −9.39 to − 3.95). The ultrasound-guided sTAP group also showed significantly lower pain scores. Incidence of PONV did not significantly differ between the 2 groups.

Conclusions:

We conclude that there is low to moderate evidence to advocate that ultrasound-guided sTAP block has better analgesic effects than WI in patients undergoing LC. Further trials are needed with robust methodology and clearly defined outcomes.
The evolution of Pemphigus publications: A bibliometric analysis with research trends and global productivity
Authors: Öztekin Aynure , Öztekin Coşkun
Published: May 2024

Despite an increase in global research on the subject of Pemphigus, which seriously affects patient health and quality of life, there is no bibliometric research on this subject in literature to date. The aim of this study was to conduct a holistic analysis of scientific articles published on Pemphigus, using bibliometric methods. Articles published on the subject of Pemphigus between 1980 and 2021 were downloaded from the web of science (WoS) database and analyzed using various statistical methods. To determine trend subjects, collaboration between countries, and the most effective studies with citation analyses, visual network maps were obtained with bibliometric analyses. A total of 3034 articles were analyzed. The 3 countries making the greatest contribution to literature were the USA (n:831, 27.3%), Japan (n:402, 13.2%), and Germany (n:221, 7.2%). The 3 most active institutions were Keio University (n:163, 5.3%), Kurume University (n:130, 4.2%) and Tel Aviv University (n:107, 3.5%). The 3 journals publishing the most articles were the British Journal of Dermatology (n: 88), Journal of the American Academy of Dermatology (n:171) and the Journal of Investigative Dermatology (n:143). The 3 leading journals according to the mean number of citations (NC) per article (citation count: CC) were the New England Journal of Medicine (CC:246), the Lancet (CC:143) and the Journal of Cell Biology (CC:133). The author with the most articles published was Hashimoto Takashi (n.168, 5.5%). As a result of cluster analysis, it was seen that 9 different main clusters had been studied on Pemphigus subjects to date (1: desmoglein, 2: paraneoplastic Pemphigus (PNP) – Pemphigus types-desmosome, 3: desmoglein 1 ve 3-autoimmunity, 4: treatment-rituximab, 5: acantholysis-apoptosis, 6: quality of life-remission-relapse, 7: autoantibodies, 8: epidemiology-mortality, 9: corticosteroids). The most commonly studied subjects were determined to be pemphigus vulgaris (PV), pemphigus foliaceus (PF), autoimmunity, rituximab, PNP, desmoglein (desmoglein3-desmoglein1), autoantibodies, acantholysis, autoantibody, treatment, autoimmune disease, desmosome, ELISA, and immunofluorescence. The primary trending topic was rituximab drug, which is used in the treatment of Pemphigus. The other most studied trend topics were azathioprine drug used in treatment, intravenous immunoglobulin treatment, quality of life, mortality rates, Pemphigus herpetiformis, and wound healing.
Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study
Authors: Liu Xing , Sun Pengcheng , Bao Xuejie , Cao Yanqi , Wang Liying , Wang Qi
Published: May 2024

The purpose of this study is to investigate the potential mechanisms of Chinese herbs for the treatment of insomnia using a combination of data mining, network pharmacology, and molecular-docking validation. All the prescriptions for insomnia treated by the academician Qi Wang from 2020 to 2022 were collected. The Ancient and Modern Medical Case Cloud Platform v2.3 was used to identify high-frequency Chinese medicinal herbs and the core prescription. The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were utilized to predict the effective active components and targets of the core herbs. Insomnia-related targets were collected from 4 databases. The intersecting targets were utilized to build a protein–protein interaction network and conduct gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the STRING database, Cytoscape software, and clusterProfiler package. Gene chip data (GSE208668) were obtained from the Gene Expression Omnibus database. The limma package was applied to identify differentially expressed genes (DEGs) between insomnia patients and healthy controls. To create a “transcription factor (TF)-miRNA-mRNA” network, the differentially expressed miRNAs were entered into the TransmiR, FunRich, Targetscan, and miRDB databases. Subsequently, the overlapping targets were validated using the DEGs, and further validations were conducted through molecular docking and molecular dynamics simulations. Among the 117 prescriptions, 65 herbs and a core prescription were identified. Network pharmacology and bioinformatics analysis revealed that active components such as β-sitosterol, stigmasterol, and canadine acted on hub targets, including interleukin-6, caspase-3, and hypoxia-inducible factor-1α. In GSE208668, 6417 DEGs and 7 differentially expressed miRNAs were identified. A “TF-miRNA-mRNA” network was constructed by 4 “TF-miRNA” interaction pairs and 66 “miRNA-mRNA” interaction pairs. Downstream mRNAs exert therapeutic effects on insomnia by regulating circadian rhythm. Molecular-docking analyses demonstrated good docking between core components and hub targets. Molecular dynamics simulation displayed the strong stability of the complex formed by small molecule and target. The core prescription by the academician Qi Wang for treating insomnia, which involves multiple components, targets, and pathways, showed the potential to improve sleep, providing a basis for clinical treatment of insomnia.
Causal relationship between hypertension and risk of constipation: A 2-way 2-sample Mendelian randomization study
Authors: Wang Rong , Sun Huiying , Yang Ting , Xu Junfeng
Published: May 2024

Patients with hypertension have a higher risk of having constipation and vice versa. The causal association between these 2 variables is not proven. We performed a retrospective Mendelian randomization analysis to determine the causal association between constipation and hypertension. Two-sample 2-way Mendelian randomization analysis was used. Genetic variants for constipation were derived from genome-wide association study data of European origin (15,902 cases and 395,721 controls). Corresponding genetic associations for hypertension were derived from European ancestry GWAS data (54,358 cases and 408,652 controls). Genetic susceptibility to hypertension was associated with an increased risk of constipation (OR: 3.459, 95% CI: 1.820–6.573, P < .001). In an inverse Mendelian randomization analysis, no causal effect of constipation on hypertension was found (OR: 0.999, 95% CI: 0.987–1.011, P = .834). In sensitivity analyses, these associations persisted and no multiple effects were found. This study suggests that there is a causal relationship between hypertension and constipation and that hypertension may increase the risk of developing constipation.
Value of 2D speckle tracking technique combined with real-time 3-dimensional echocardiography in the evaluation of the right atrial function in patients with 3-branch coronary artery disease without myocardial infarction
Authors: Zhang Siran , Zhou Qiao , Li Xiya , Wang Yifan , Ma Le , Huang Dongmei , Li Guangsen
Published: May 2024

To evaluate the right atrial function in patients with 3-branch coronary artery disease (TBCAD) without myocardial infarction by 2D speckle tracking echocardiography (2D-STE) combined with real-time 3-dimensional echocardiography (RT-3DE). Fifty-six patients admitted to our hospital without myocardial infarction with TBCAD were selected. We divided them into 2 groups according to the coronary angiography results: 28 patients in group B (the rate of stenosis is 50% ~< 75%); 28 patients in group C (the rate of stenosis is ≥75%); in addition, 30 healthy volunteers were screened as group A. All subjects underwent RT-3DE to obtain the right atrial volume (RAVmax, RAVmin, and RAVp), and then we calculated the right atrial passive and active ejection fraction (RAPEF, RAAEF), and maximum volume index (RAVImax). In addition, to measure the strain rates (RASRs, RASRe, RASRa) of the right atrium during systole, early diastole, and late diastole, 2D-STE was applied. Correlations between the 2D-STE parameters and the results of N-terminal pro-brain natriuretic peptide (NT-proBNP) and Gensini scores were analyzed by Pearson linear analysis. Compared with group A, RAPEF and RASRe were reduced, while RAAEF and RASRa were elevated in group B (P < .05). RAPEF, RASRs, RASRe, and RASRa were decreased compared with groups A and B, while RAVmax, RAVmin, RAVp, RAVImax, and RAAEF were increased in group C (P < .05). There was a significant correlation between 2D-STE parameters and the results of NT-proBNP and Gensini scores (P < .05). The storage, conduit, and pump functions of the right atrium are reduced in patients with 3-branch coronary artery disease without myocardial infarction; 2D-STE combined with RT-3DE is valuable in the evaluation of the right atrium in patients with coronary artery disease.
Causes and outcomes of non-chemotherapy induced neutropenic fever in hospitalized adults: An observational study
Authors: Crooker Kyle G. , Stedman Eleanor R. , Hitt Juvena R. , Tompkins Bradley J. , Repp Allen B.
Published: May 2024

Neutropenic fever in adults undergoing chemotherapy for cancer treatment is a medical emergency and has been the focus of numerous studies. However, there is a paucity of data about non-chemotherapy induced neutropenic fever (non-CINF). We retrospectively reviewed 383 adults with neutropenic fever hospitalized at one academic medical center between October 2015 and September 2020 to characterize the frequency, causes, and outcomes of non-CINF. Twenty-six percent of cases of neutropenic fever were non-chemotherapy induced. Among these, the major causes of neutropenia were hematologic malignancy, infection, and rheumatologic disease, and the major causes of fever were infections. Patients with non-CINF had a higher 30-day mortality than those with chemotherapy induced neutropenic fever (25% vs 13%, P = .01). Non-CINF constituted > 25% of neutropenic fever events in hospitalized adults and was associated with a high mortality rate.
Arthroscopic rotator cuff repair combined with platelet-rich plasma products can reduce the rate of retearing and improve clinical outcomes: A meta-analysis of randomized controlled trials
Authors: Shen Zhe , Ye Xiaoang , He Yawen , Shen Gaobo , Xu Kuangying , Zhang Bingbing , Wu Lianguo
Published: May 2024

Background:

Although several studies on the potential benefits of protein-rich plasma (PRP) therapy for rotator cuff injuries have been published, the results have been conflicting. Therefore, this study aimed to determine whether PRP is beneficial for the prevention of retears after arthroscopic rotator cuff repair (ARCR).

Methods:

Two reviewers conducted independent literature searches based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials (RCTs) comparing a PRP treatment group with a control group were included. The quality of evidence was assessed using the Cochrane Collaboration Risk of Bias Tool. Clinical outcomes were compared using the risk ratio (RR) for dichotomous variables and weighted mean difference (WMD) for continuous variables. Statistical significance was set atP < .05.

Results:

This review included 21 RCTs (1359 patients). Significant results were noted in favor of PRP treatment compared with controls based on retearing rates (16.5% vs 23.6%, respectively;P = .002) and the Constant score in the short term (WMD: 1.98; 95% confidence interval [CI], 0.27–3.70; I2 = 0%;P = .02), medium term and long term (WMD: 2.56 [95% CI: 1.57–3.55]; I2 = 2%;P < .001); the University of California, Los Angeles score in the short term (WMD: 1.14 [95% CI: 0.43–1.85]; I2 = 25%;P = .002) but not in the medium and long term (WMD: 0.66 [95% CI: –0.16 to 1.48]; I2 = 57%;P = .11); and the visual analog scale score in the short term (WMD: –0.63 [95% CI: –0.83 to–0.43]; I2 = 41%;P < .001), medium and long term (WMD: –0.12 [95% CI: –0.19 to–0.05]; I2 = 0%;P = .008). There was no significant difference in American Shoulder and Elbow Surgeons scores between the treatment and control groups in the short term (WMD: –0.48 [95% CI: –2.80 to 1.85]; I2 = 22%;P = .69) or medium and long term (WMD: 0.92 [95% CI: –1.56 to 3.39]; I2 = 40%;P = .47).

Conclusion:

Intraoperative use of PRP reduces the risk of rotator cuff repair failure, improves clinical outcomes, and reduces recurrence rates.
Mindfulness and Interoceptive Awareness
Authors: Sala Margaret , Schanzer Sophie , Morris Claudia
Published: May 2024

Higher trait mindfulness is correlated with higher interoceptive awareness. However, there is a gap in understanding which mindfulness dimensions connect to which interoceptive awareness dimensions. This study (N = 1005) used network analysis to identify central and bridge nodes driving the linkage between mindfulness and interoceptive awareness. Central nodes included trusting body sensations, feeling a sense of calm when bringing awareness to the body, the ability to refocus one's attention from thinking to sensing the body, and the ability to accept all emotions. Bridge nodes included noticing how food and drink affect thoughts, bodily sensations, and emotions; staying alert to the sensations of the body when taking a shower; and noticing and letting go of distressing thoughts and feelings. Future research studies should explore whether mindfulness-based interventions may be more effective by targeting observations of sensations related to eating and the body as well as noticing and letting go of distressing thoughts and feelings.
Association between tight junction proteins and cognitive performance in untreated persons with HIV
Authors: Bai Francesca , Bono Valeria , Borghi Lidia , Bonazza Federica , Falcinella Camilla , Vitaletti Virginia , Miraglia Federica , Trunfio Mattia , Calcagno Andrea , Cusato Jessica , Vegni Elena , d’Arminio Monforte Antonella , Marchetti Giulia
Published: May 2024

Background:

HIV-associated neurocognitive disorders (HAND) still affects persons with HIV (PWH) and their pathogenesis is not completely understood. We aimed to explore the association between plasma and cerebrospinal fluid (CSF) markers of blood–brain barrier (BBB) impairment and HAND in untreated PWH.

Design:

Cross-sectional study.

Methods:

We enrolled untreated PWH, who underwent blood examinations and lumbar puncture to measure inflammation (IL-15, TNF-α), BBB damage (zonulin and tight junction proteins, tight junction proteins: occludin, claudin-5) and endothelial adhesion molecules (VCAM-1, ICAM-1). A comprehensive neurocognitive battery was used to diagnose HAND (Frascati criteria).

Results:

Twenty-one patients (21/78, 26.9%) patients presented HAND (100% ANI). HAND patients displayed more frequently non-CNS AIDS-defining conditions, lower nadir CD4+T cells and increased CD4+T-cell exhaustion (lower CD4+CD127+and CD4+CD45RA+T-cell percentages), in comparison to individuals without cognitive impairment. Furthermore, HAND was characterized by higher plasma inflammation (IL-15) but lower CSF levels of biomarkers of BBB impairment (zonulin and occludin). The association between BBB damage with HAND was confirmed by fitting a multivariable logistic regression. CSF/plasma endothelial adhesion molecules were not associated with HAND but with a poor performance in different cognitive domains.

Conclusion:

By showing heightened inflammation and BBB impairment, our study suggests loss of BBB integrity as a possible factor contributing to the development of HAND in untreated PWH.
Association between antioxidant metabolites and N-terminal fragment brain natriuretic peptides in insulin-resistant individuals
Authors: Anwardeen Najeha , Naja Khaled , Elrayess Mohamed A.
Published: May 2024

Objectives

Oxidative stress plays a pivotal role in the development of metabolic syndrome, including heart failure and insulin resistance. The N-terminal fragment of brain natriuretic peptide (NT-proBNP) has been associated with heightened oxidative stress in heart failure patients. Yet, its correlation with insulin resistance remains poorly understood. Our objective is to investigate the association between oxidative stress markers and NT-proBNP levels in insulin-resistant individuals.

Methods

In this cross-sectional study involving 393 participants from the Qatar Biobank, clinical and metabolic data were collected, and the association between NT-proBNP and 72 oxidative stress metabolites was compared between insulin-sensitive and insulin-resistant individuals.

Results

Our results showed significantly lower NT-proBNP levels in insulin-resistant individuals (median = 17 pg/ml; interquartile range = 10.3–29) when compared to their insulin-sensitive counterparts (median = 31 pg/ml; interquartile range = 19–57). Moreover, we revealed notable associations between NT-proBNP levels and antioxidant metabolic pathways, particularly those related to glutathione metabolism, in insulin-resistant, but not insulin-sensitive individuals.

Conclusion

The significant decrease in NT-proBNP observed in individuals with insulin resistance may be attributed to a direct or indirect enhancement in glutathione production, which is regarded as a compensatory mechanism against oxidative stress. This study could advance our understanding of the interplay between oxidative stress during insulin resistance and cardiovascular risk, which could lead to novel therapeutic approaches for managing cardiovascular diseases. Further investigations are needed to assess the practical utility of these potential metabolites and understand the causal nature of their association with NT-proBNP in the etiology of insulin resistance.
Phase II study of nivolumab and ipilimumab for treatment of metastatic/recurrent adenoid cystic carcinoma (ACC) of all anatomic sites of origin and other malignant salivary gland tumors
Authors: Chae Young Kwang , Duan Richard , Chung Liam Il-Young , Oh Youjin , Alexiev Borislav , Shin Sangwon , Kim Sukjun , Helenowski Irene , Matsangou Maria , Villaflor Victoria , Mahalingam Devalingam
Published: May 2024

Objective

Dual checkpoint inhibitor therapy with nivolumab and ipilimumab has been FDA-approved for a number of cancer sites. However, their role in the treatment of ACC and other salivary gland carcinomas is not well established.

Methods and analysis

We performed a Simon’s two-stage prospective single-institution phase II clinical trial of nivolumab with ipilimumab. Two cohorts were analyzed: patients with metastatic/recurrent ACC and patients with other salivary gland cancers. The primary endpoint was median progression-free survival (PFS); secondary endpoints were overall response rate (ORR), overall survival (OS), and toxicity.

Results

Patients with ACC (n=19) and other salivary gland carcinomas (total n=5) were enrolled. The patients with ACC had median OS 30.0 months (95% CI 15.3-NR months), median PFS 8.3 months (95% CI 5.5-30.0 months), and disease control rate (DCR) 53% (10/19). The ORR in the ACC group was 5% (CR 0%, n=0; confirmed PR 5%, n=1), with one patient having continued stable disease at the time of trial conclusion. The patients with other salivary gland cancers had median OS 10.4 months (95% CI 6.21-NR months), median PFS 6.21 months (95% CI 2.83-NR months), and DCR 40% (2/5). The ORR in this cohort was 0%.

Conclusion

In patients with recurrent or metastatic ACC and other salivary gland neoplasms, combination nivolumab with ipilimumab resulted in moderate disease control. Further studies are warranted to validate our findings.

Trial number:NCT03146650
An allometric study of the contribution of prostrate stems to belowground development of juvenileFagus crenata
Authors: Shimizu Yutaro , Tondokoro Yudai , Ida Hideyuki
Published: May 2024

Prostrate stems represent an important morphological component ofFagus crenata(Siebold’s beech). This unique stem-bending growth strategy has led to the dominance of this tree species in regions with heavy snowfall along the Sea of Japan. We investigated the early-stage aboveground–belowground dynamics ofF. crenataby applying allometric scaling theory to analyze morphological development in saplings (aged 3–20 years). Samples were collected from 25 trees in three forests in Nagano, central Japan. The scaling exponent (b) demonstrated an increase in the fraction of aboveground biomass (i.e., dry mass) in relation to the overall surface area (aboveground,b= 0.748; belowground,b= 0.626) and biomass (aboveground,b= 1.087; belowground,b= 0.983). These values are highly consistent with recent field observations by other researchers. Aboveground biomass growth was supported by the increasing role of prostrate stems in belowground development (b= 1.114). Despite its extension belowground, the growth properties of the prostrate stem may be identical to those of shoots, as both are directly influenced by nutrient sources above the germination point. Our findings highlight the significance of the prostrate stem in supporting beech survival in areas with heavy snowfall.
Hydrogel-embedded precision-cut lung slices supportex vivoculture ofin vivo-induced premalignant lung lesions
Authors: Hauer Caroline , Blomberg Rachel , Sompel Kayla , Magin Chelsea M. , Tennis Meredith A.
Published: May 2024

Lung cancer is the leading cause of global cancer death and prevention strategies are key to reducing mortality. Medical prevention may have a larger impact than treatment on mortality by targeting high-risk populations and reducing their lung cancer risk. Premalignant lesions (PMLs) that can be intercepted by prevention agents are difficult to study in humans but easily accessible in murine preclinical carcinogenesis studies. Precision-cut lung slices (PCLS) are underutilized as anex vivomodel for lung cancer studies due to limited culture time. Embedding PCLS within bioengineered hydrogels extends PCLS viability and functionality for up to six weeks. Here, we embedded PCLS generated from urethane-induced murine PMLs in cell-degradable and non-degradable hydrogels to study viability and activity of the tissues over six weeks. PMLs in hydrogel-embedded PCLS maintained viability, gene expression, and proliferation. Treatment of hydrogel-embedded PCLS containing urethane-induced PMLs with iloprost, a known lung cancer prevention agent, recapitulatedin vivogene expression and activity. These studies also showed that iloprost reduced proliferation and PML size in hydrogel-embedded PCLS, with some differences based on hydrogel formulation and suggested that hydrogel-embedded PCLS models may support long-term culture ofin vivogenerated PMLs to improve preclinical studies of lung cancer and prevention agents.
Reproducible differentiation of pure ovarian support cells from clinical-grade hiPSCs as a novel infertility treatment
Authors: Paulsen Bruna , Barrachina Ferran , Noblett Alexander D. , Johnson Mark , Kats Simone , Piechota Sabrina , Marchante Maria , Figueroa Alexandra B. , Potts Kathryn S , Rockwell Graham , Giovannini Alexa , Kramme Christian C.
Published: May 2024

In vitro maturation (IVM) is an infertility treatment used during in vitro fertilization (IVF) procedures in which immature oocytes are matured outside the body, limiting the excessive hormone doses required for retrieval of ready-to-fertilize oocytes. To overcome the historically low embryo formation rate associated with IVM, we have recently demonstrated that co-culture of hiPSC-derived ovarian support cells (OSCs) yielded higher rates of oocyte maturation and euploid embryo formation, by mimicking the complex ovarian environment in vitro, offering a novel solution to overcome the IVM main limitation. To translate this process into clinics, we sourced and engineered a compliant female clinical-grade (CG) hiPSC line to derive OSCs with similar quality attributes and clinical outcomes to results previously demonstrated with a research hiPSC line. We further optimized our manufacturing protocols to enable increased scale and substituted reagents with appropriate higher-quality alternatives. This strategic approach to product development has successfully met scalable manufacturing needs and ultimately resulted in a product of improved reproducibility, purity, and efficacy. Our findings support the use of a similar strategy to fine-tune hiPSC-derived products facilitating translation to clinical applications.
Small Extracellular Vesicle Signaling and Mitochondrial Transfer Reprograms T Helper Cell Function in Human Asthma
Authors: Hough Kenneth P. , Trevor Jennifer L. , Chacko Balu K. , Strenkowski John G. , Wang Yong , Goliwas Kayla F. , Bone Nathaniel B. , Kim Young-il , Holmes Renita , Vang Shia , Pritchard Alexandra , Chin Jay , Bodduluri Sandeep , Antony Veena B. , Tousif Sultan , Athar Mohammad S. , Chanda Diptiman , Mitra Kasturi , Zmijewski Jaroslaw , Zhang Jianhua , Duncan Steven R. , Thannickal Victor J. , Gabrielsson Susanne , Darley-Usmar Victor M. , Deshane Jessy S.
Published: May 2024

Rationale: Asthma is a chronic inflammatory disease of the airways that involves crosstalk between myeloid-derived regulatory cells (MDRCs) and CD4+ T cells. Although small extracellular vesicles (sEVs) are known to mediate cell-cell communication, the role of sEV signaling via mitochondria in perpetuating asthmatic airway inflammation is unknown. Objectives: We investigated the effects of MDRC-derived exosomes on dysregulated T cell responses in asthmatics. Methods: Small extracellular vesicles isolated from bronchoalveolar lavage fluid or airway MDRCs of mild to moderate asthmatics or healthy controls were co-cultured with autologous peripheral and airway CD4+ T lymphocytes. sEV internalization, sEV-mediated transfer of mitochondria targeted GFP to T cells, sEV mitochondrial signaling, and subsequent activation, proliferation and polarization of CD4+ T lymphocytes to Th1, Th2 and Th17 subsets were assessed. Measurements and main results: Airway MDRC-derived sEVs from asthmatics mediated T cell receptor engagement and transfer of mitochondria that induced antigen-specific activation and polarization into Th17 and Th2 cells, drivers of chronic airway inflammation in asthma. CD4+ T cells internalized sEVs containing mitochondria predominantly by membrane fusion, and blocking mitochondrial oxidant signaling in MDRC-derived exosomes mitigated T cell activation. Reactive oxygen species-mediated signaling that elicited T cell activation in asthmatics was sEV-dependent. A Drp1-dependent mitochondrial fission in pro-inflammatory MDRCs promoted mitochondrial packaging within sEVs, which then co-localized with the polarized actin cytoskeleton and mitochondrial networks in the organized immune synapse of recipient T cells. Conclusions: Our studies indicate a previously unrecognized role for mitochondrial fission and exosomal mitochondrial transfer in dysregulated T cell activation and Th cell differentiation in asthma which could constitute a novel therapeutic target.