bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between anatomical characteristics of pulmonary veins and atrial fibrillation recurrence after radiofrequency catheter ablation: a systematic review and meta-analysis
Authors: Qi Dan , Zhang Jianjun 
Published: September 2023

BackgroundThe aim of the current study was to investigate the potential relationship between anatomical characteristics of pulmonary veins (PVs) and atrial fibrillation recurrence (AFR) following radiofrequency catheter ablation (RFCA), specifically focusing on PV diameter and cross-sectional orifices index (CSOA). The analysis was based on a comprehensive review of currently available literature, providing valuable insights for the prevention and treatment of AFR.MethodsData was collected from five databases, including PubMed, MEDLINE, EMBASE, and Cochrane, spanning the period from 2004 to October 2022. The search strategy utilized Medical Subject Headings (MeSH) terms related to PV diameter, PV size, PV anatomy, and AFR. Indicators of PV diameter and CSOA from the included studies were collected and analyzed, with Weight mean difference (WMD) and 95% confidence intervals (CIs) representing continuous variables.ResultsThe meta-analysis included six studies. The results revealed that patients with AFR had a significant larger mean PV diameter compared to those without AFR (MD 0.33; 95% CI: 0.01, 0.66; P = 0.04; I2 = 33.80%). In a meta-analysis of two studies involving a total of 715 participants, we compared the diameters of the left superior pulmonary vein (LSPV), left inferior pulmonary vein (LIPV), right superior pulmonary vein (RSPV), right inferior pulmonary vein (RIPV) between patients with AFR and patients without AFR. The results showed that there were no statistically significant differences between the two groups in any of the four data items (all P &gt; 0.05). Additionally, the pooled estimate revealed that LSPV-CSOA, LIPV-COSA, RSPV-COSA, and RIPV-CSOA were greater in the AFR group compared to the non-AFR group, but the differences were not statistically significant (all P &gt; 0.05).ConclusionWe found evidence supporting the notion that the PV diameter of patients who experienced AFR after RFCA was significantly larger than that of patients without AFR. The findings suggested that the PV diameter could serve as a potential predictor of the risk of AFR following RFCA.
Strategies in activating lymphatic system on symptom distress and health-related quality of life in patients with heart failure: secondary analysis of a pilot randomized controlled trial
Authors: Liu Ruixia , Fang Jinbo , Fu Mei R. , Meng Qingtong , Li Minlu , Zhang Xiaoxia , Allred Sarah R. , Li Yuan 
Published: September 2023

BackgroundAbnormal interstitial fluid accumulation remains the major cause for patients with heart failure (HF) to endure a myriad of distressing symptoms and a decline in their health-related quality of life (HRQoL). The lymphatic system is essential in regulating fluid balance within the interstitial compartment and has recently been recognized as an important target for the prevention and mitigation of congestion. This study aimed to investigate the effects of exercises in activating lymphatic system on symptom distress and HRQoL among patients with HF.Methods and resultsThis was a pre-determined, secondary analysis of the TOLF-HF [The-Optimal-Lymph-Flow for Heart Failure (TOLF-HF)] study, a two-arm pilot randomized controlled trial evaluating the preliminary effects of the lymphatic exercise intervention in enhancing interstitial decongestion among patients with HF. Participants were randomized to receive either a four-week TOLF-HF program in addition to standard care or standard care alone. The Chinese version of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was employed to measure symptom distress and HRQoL before and after the intervention. Data analyses included descriptive statistics, the independent sample t-test, Pearson’s chi-square test, the Mann-Whitney U test, and covariance analysis. Of the 66 patients enrolled, 60 completed the study. The study results exhibited that the TOLF-HF intervention were effective in alleviating both physical and psychological symptom distress. The intervention group yielded significantly lower MLHFQ total scores in comparison to the control group. The odd ratio of achieving meaningful improvement in HRQoL in TOLF-HF group was 2.157 times higher than those in the control group.ConclusionsThe TOLF-HF program focusing on activating lymphatic system was effective in alleviating physical and psychological symptom distress as well as improving HRQoL for patients with HF. The tolerability, feasibility, and effectiveness of the TOLF-HF intervention make it a promising intervention for patients to manage HF.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier (ChiCTR2000039121).
Nickel as a potential disruptor of thyroid function: benchmark modelling of human data
Authors: Maric Djurdjica , Baralic Katarina , Javorac Dragana , Mandic-Rajcevic Stefan , Zarkovic Milos , Antonijevic Biljana , Djukic-Cosic Danijela , Bulat Zorica , Djordjevic Aleksandra Buha 
Published: September 2023

IntroductionNickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept.MethodsNi concentration was measured by ICP-MS method, while CLIA was used for serum hormone determination. SPINA Thyr software was used to calculate SPINA-GT and SPINA-GD parameters. BMD analysis was performed by PROAST software (70.1). The limitations of this study are the small sample size and the uneven distribution of healthy and unhealthy subjects, limited confounding factors, as well as the age of the subjects that could have influenced the obtained results.Results and discussionThe highest median value for blood Ni concentration was observed for the male population and amounted 8,278 µg/L. Accordingly, the statistically significant correlation was observed only in the male population, for Ni-fT4 and Ni-SPINA-GT pairs. The existence of a dose-response relationship was established between Ni and all the measured parameters of thyroid functions in entire population and in both sexes. However, the narrowest BMD intervals were obtained only in men, for Ni - SPINA-GT pair (1.36-60.9 µg/L) and Ni - fT3 pair (0.397-66.8 µg/L), indicating that even 78.68 and 83.25% of men in our study might be in 10% higher risk of Ni-induced SPINA-GT and fT3 alterations, respectively. Due to the relationship established between Ni and the SPINA-GT parameter, it can be concluded that Ni has an influence on the secretory function of the thyroid gland in men. Although the further research is required, these findings suggest possible role of Ni in thyroid function disturbances.
Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and meta-analysis
Authors: Moleti Mariacarla , Aversa Tommaso , Crisafulli Salvatore , Trifirò Gianluca , Corica Domenico , Pepe Giorgia , Cannavò Laura , Di Mauro Maria , Paola Giuseppe , Fontana Andrea , Calapai Fabrizio , Cannavò Salvatore , Wasniewska Malgorzata 
Published: September 2023

ObjectiveDifferentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0–19 years.MethodsThe systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC.ResultsAfter the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33–0.59) and 0.07 (95% CI: 0.02–0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities.ConclusionOur data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.
Comprehensive analysis of ceRNA network composed of circRNA, miRNA, and mRNA in septic acute kidney injury patients based on RNA-seq
Authors: Ma Si-Rong , Ma Qi , Ma Ya-Nan , Zhou Wen-Jie 
Published: September 2023

Background: Sepsis is a complex, life-threatening clinical syndrome that can cause other related diseases, such as acute kidney injury (AKI). Circular RNA (circRNA) is a type of non-coding RNA with a diverse range of functions, and it plays essential roles in miRNA sponge. CircRNA plays a huge part in the development of various diseases. CircRNA and the competing endogenous RNA (ceRNA) regulatory network are unknown factors in the onset and progression of septic AKI (SAKI). This study aimed to clarify the complex circRNA-associated regulatory mechanism of circRNAs in SAKI.Methods: We collected 40 samples of whole blood of adults, including 20 cases of SAKI and 20 cases of healthy controls. Moreover, five cases were each analyzed by RNA sequencing, and we identified differentially expressed circRNA, miRNA, and mRNA (DEcircRNAs, DEmiRNAs, and DEmRNAs, respectively). All samples were from SAKI patients with intraperitoneal infection.Results: As a result, we screened out 236 DEcircRNAs, 105 DEmiRNAs, and 4065 DEmRNAs. Then, we constructed two co-expression networks based on RNA–RNA interaction, including circRNA–miRNA and miRNA–mRNA co-expression networks. We finally created a circRNA–miRNA–mRNA regulation network by combining the two co-expression networks. Functional and pathway analyses indicated that DEmRNAs in ceRNA were mostly concentrated in T cell activation, neutrophils and their responses, and cytokines. The protein–protein interaction network was established to screen out the key genes participating in the regulatory network of SAKI. The hub genes identified as the top 10 nodes included the following: ZNF727, MDFIC, IFITM2, FOXD4L6, CIITA, KCNE1B, BAGE2, PPIAL4A, USP17L7, and PRSS2.Conclusion: To our knowledge, this research is the first study to describe changes in the expression profiles of circRNAs, miRNAs, and mRNAs in patients with SAKI. These findings provide a new treatment target for SAKI treatment and novel ideas for its pathogenesis.
Comprehensive immunophenotyping of solid tumor-infiltrating immune cells reveals the expression characteristics of LAG-3 and its ligands
Authors: Garman Bradley , Jiang Can , Daouti Sherif , Kumar Sanah , Mehta Priyanka , Jacques Miye K. , Menard Laurence , Manjarrez-Orduno Nataly , Dolfi Sonia , Mukherjee Piali , Rai Sharmila Chamling , Lako Ana , Koenitzer Jennifer D. , David Justin M. 
Published: September 2023

BackgroundImmune cell expression profiling from patient samples is critical for the successful development of immuno-oncology agents and is useful to understand mechanism-of-action, to identify exploratory biomarkers predictive of response, and to guide treatment selection and combination therapy strategies. LAG-3 is an inhibitory immune checkpoint that can suppress antitumor T-cell responses and targeting LAG-3, in combination with PD-1, is a rational approach to enhance antitumor immunity that has recently demonstrated clinical success. Here, we sought to identify human immune cell subsets that express LAG-3 and its ligands, to characterize the marker expression profile of these subsets, and to investigate the potential relationship between LAG-3 expressing subsets and clinical outcomes to immuno-oncology therapies.MethodsComprehensive high-parameter immunophenotyping was performed using mass and flow cytometry of tumor-infiltrating lymphocytes (TILs) and peripheral blood mononuclear cells (PBMCs) from two independent cohorts of samples from patients with various solid tumor types. Profiling of circulating immune cells by single cell RNA-seq was conducted on samples from a clinical trial cohort of melanoma patients treated with immunotherapy.ResultsLAG-3 was most highly expressed by subsets of tumor-infiltrating CD8 T central memory (TCM) and effector memory (TEM) cells and was frequently co-expressed with PD-1. We determined that these PD-1+ LAG-3+ CD8 memory T cells exhibited a unique marker profile, with greater expression of activation (CD69, HLA-DR), inhibitory (TIM-3, TIGIT, CTLA-4) and stimulatory (4-1BB, ICOS) markers compared to cells that expressed only PD-1 or LAG-3, or that were negative for both checkpoints. In contrast to tumors, LAG-3 expression was more limited in circulating immune cells from healthy donors and solid tumor patients. Additionally, we found abundant expression of the LAG-3 ligands MHC-II and galectin-3 in diverse immune cell types, whereas FGL1 and LSECtin were minimally expressed by immune cells in the tumor microenvironment (TME). Lastly, we found an inverse relationship between baseline and on-treatment levels of circulating LAG3 transcript-expressing CD8 memory T cells and response to combination PD-1 and CTLA-4 blockade in a clinical trial cohort of melanoma patients profiled by scRNAseq.ConclusionsThese results provide insights into the nature of LAG-3- and ligand-expressing immune cells within the TME, and suggest a biological basis for informing mechanistic hypotheses, treatment selection strategies, and combination immunotherapy approaches to support continued development of dual PD-1 and LAG-3 blockade.
Expanded Hemodialysis ameliorates uremia-induced impairment of vasculoprotective KLF2 and concomitant proinflammatory priming of endothelial cells through an ERK/AP1/cFOS-dependent mechanism
Authors: Zhao Hongfan , Wu Dashan , Gyamfi Michael Adu , Wang Pinchao , Luecht Christian , Pfefferkorn Anna Maria , Ashraf Muhammad Imtiaz , Kamhieh-Milz Julian , Witowski Janusz , Dragun Duska , Budde Klemens , Schindler Ralf , Zickler Daniel , Moll Guido , Catar Rusan 
Published: September 2023

AimsExpanded hemodialysis (HDx) therapy with improved molecular cut-off dialyzers exerts beneficial effects on lowering uremia-associated chronic systemic microinflammation, a driver of endothelial dysfunction and cardiovascular disease (CVD) in hemodialysis (HD) patients with end-stage renal disease (ESRD). However, studies on the underlying molecular mechanisms are still at an early stage. Here, we identify the (endothelial) transcription factor Krüppel-like factor 2 (KLF2) and its associated molecular signalling pathways as key targets and regulators of uremia-induced endothelial micro-inflammation in the HD/ESRD setting, which is crucial for vascular homeostasis and controlling detrimental vascular inflammation.Methods and resultsFirst, we found that human microvascular endothelial cells (HMECs) and other typical endothelial and kidney model cell lines (e.g. HUVECs, HREC, and HEK) exposed to uremic serum from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation II (PERCI-II) crossover clinical trial - comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes - exhibited strongly reduced expression of vasculoprotective KLF2 with HF dialyzers, while dialysis with MCO dialyzers led to the maintenance and restoration of physiological KLF2 levels in HMECs. Mechanistic follow-up revealed that the strong downmodulation of KLF2 in HMECs exposed to uremic serum was mediated by a dominant engagement of detrimental ERK instead of beneficial AKT signalling, with subsequent AP1-/c-FOS binding in the KLF2 promoter region, followed by the detrimental triggering of pleiotropic inflammatory mediators, while the introduction of a KLF2 overexpression plasmid could restore physiological KLF2 levels and downmodulate the detrimental vascular inflammation in a mechanistic rescue approach.ConclusionUremia downmodulates vasculoprotective KLF2 in endothelium, leading to detrimental vascular inflammation, while MCO dialysis with the novel improved HDx therapy approach can maintain physiological levels of vasculoprotective KLF2.
SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition
Authors: Limoges Marc-André , Quenum Akouavi Julite Irmine , Chowdhury Mohammad Mobarak Hussain , Rexhepi Fjolla , Namvarpour Mozhdeh , Akbari Sara Ali , Rioux-Perreault Christine , Nandi Madhuparna , Lucier Jean-François , Lemaire-Paquette Samuel , Premkumar Lakshmanane , Durocher Yves , Cantin André , Lévesque Simon , Dionne Isabelle J. , Menendez Alfredo , Ilangumaran Subburaj , Allard-Chamard Hugues , Piché Alain , Ramanathan Sheela 
Published: September 2023

BackgroundFollowing SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic.MethodsThe study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA.ResultsThe frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups.ConclusionsThe antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens.
Identification of SKOR2 IgG as a novel biomarker of paraneoplastic neurologic syndrome
Authors: Rezk Mohamed , Pittock Sean J. , Kapadia Ronak K. , Knight Andrew M. , Guo Yong , Gupta Pranjal , LaFrance-Corey Reghann G. , Zekeridou Anastasia , McKeon Andrew , Dasari Surendra , Mills John R. , Dubey Divyanshu 
Published: September 2023

IntroductionThe development of new autoantigen discovery techniques, like programmable phage immunoprecipitation sequencing (PhIP-Seq), has accelerated the discovery of neural-specific autoantibodies. Herein, we report the identification of a novel biomarker for paraneoplastic neurologic syndrome (PNS), Sloan-Kettering-Virus-Family-Transcriptional-Corepressor-2 (SKOR2)-IgG, utilizing PhIP-Seq. We have also performed a thorough clinical validation using normal, healthy, and disease/cancer control samples.MethodsStored samples with unclassified staining at the junction of the Purkinje cell and the granule cell layers were analyzed by PhIP-Seq for putative autoantigen identification. The autoantigen was confirmed by recombinant antigen-expressing cell-based assay (CBA), Western blotting, and tissue immunofluorescence assay colocalization.ResultsPhIP-Seq data revealed SKOR2 as the candidate autoantigen. The target antigen was confirmed by a recombinant SKOR-2-expressing, and cell lysate Western blot. Furthermore, IgG from both patient samples colocalized with a commercial SKOR2–specific IgG on cryosections of the mouse brain. Both SKOR2 IgG-positive patients had central nervous system involvement, one presenting with encephalitis and seizures (Patient 1) and the other with cognitive dysfunction, spastic ataxia, dysarthria, dysphagia, and pseudobulbar affect (Patient 2). They had a refractory progressive course and were diagnosed with adenocarcinoma (Patient 1: lung, Patient 2: gallbladder). Sera from adenocarcinoma patients without PNS (n=30) tested for SKOR2-IgG were negative.DiscussionSKOR2 IgG represents a novel biomarker for PNS associated with adenocarcinoma. Identification of additional SKOR2 IgG-positive cases will help categorize the associated neurological phenotype and the risk of underlying malignancy.
Monsoon-driven seasonal hypoxia along the northern coast of Oman
Authors: DiMarco Steven F. , Wang Zhankun , Chapman Piers , al-Kharusi Lubna , Belabbassi Leila , al-Shaqsi Hilal , Stoessel Marion , Ingle Stephanie , Jochens Ann E. , Howard Matthew K. 
Published: September 2023

Dissolved oxygen and current observations from a cabled ocean observatory in the Sea of Oman show that the annual recurrence of coastal hypoxia, defined as dissolved oxygen concentrations ≤63 μM, is associated with the seasonal cycle of local monsoon winds. The observations represent the first long-term (5+ years) continuous moored observations off the northern Omani coast. During the summer/fall southwest (SW) monsoon season (Jun-Nov), winds in the Sea of Oman generate ocean currents that result in coastal upwelling of subsurface waters with low dissolved oxygen concentrations. The source of the poorly oxygenated water is the oxygen minimum zone (OMZ) in the Arabian Sea, a layer approximately 1000-m thick within the 100 to 1200 m depth range, where dissolved oxygen values approach anoxia. During the winter monsoon season (Dec-Feb), the Sea of Oman winds are from the northwest, forcing strong and persistent southeast currents. These winds generate oceanic downwelling conditions along the coastal ocean that ventilate waters at depth. Possible impacts of the monsoon-driven seasonal hypoxia on local fisheries and implications due to climate change are also discussed in this study.