bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypersynchrony in sarcomeric hypertrophic cardiomyopathy: description and mechanistic approach using multimodal electro-mechanical non-invasive cartography (HSYNC study)
Authors: Réant Patricia , Bonnet Guillaume , Dubé Frédérique , Massie Charles , Reynaud Amélie , Michaud Matthieu , Duchateau Josselin , Lafitte Stéphane 
Published: June 2024

BackgroundLittle is known about left ventricular (LV) sequences of contraction and electrical activation in hypertrophic cardiomyopathy (HCM). A better understanding of the underlying relation between mechanical and electrical activation may allow the identification of predictive response criteria to right ventricular DDD pacing in obstructive patients.ObjectiveTo describe LV mechanical and electrical activation sequences in HCM patients compared to controls.Materials and methodsWe prospectively studied, in 40 HCM patients (20 obstructive and 20 non-obstructive) and 20 healthy controls: (1) mechanical activation using echocardiography at rest and cardiac magnetic resonance imaging, (2) electrical activation using 3-dimensional electrocardiographic mapping (ECM).ResultsIn echocardiography, healthy controls had a physiological apex-to-base delay (ABD) during contraction (23.8 ± 16.2 ms). Among the 40 HCM patients, 18 HCM patients presented a loss of this ABD (&lt;10 ms, defining hypersynchrony) more frequently than controls (45% vs. 5%, p = 0.017). These patients had a lower LV end-diastolic volume (71.4 ± 9.7 ml/m2 vs. 82.4 ± 14.8 ml/m2, p = 0.01), lower native T1 values (988 ± 32 ms vs. 1,028 ± 39 ms, p = 0.001) and tended to have lower LV mass (80.7 ± 23.7 g/m2 vs. 94.5 ± 25.3 g/m2, p = 0.08) compared with HCM patients that had a physiological contraction sequence. There was no significant relation between ABD and LV outflow tract obstruction. While HCM patients with a physiological contraction sequence presented an ECM close to those encountered in controls, patients with a loss of ABD presented a particular pattern of ECM with the first potential more frequently occurring in the postero-basal region.ConclusionThe LV contraction sequence can be modified in HCM patients, with a loss of the physiological ABD, and is associated with smaller LV dimensions and a particular pattern of ECM. Further research is needed to determine whether this pattern is related to an electrical substrate or is the consequence of the hypertrophied heart's specific geometry.Clinical trial registrationClinicalTrial.gov: NCT02559726.
Lung transplantation following controlled hypothermic storage with a portable lung preservation device: first multicenter European experience
Authors: Provoost An-Lies , Novysedlak Rene , Van Raemdonck Dirk , Van Slambrouck Jan , Prisciandaro Elena , Vandervelde Christelle M. , Barbarossa Annalisa , Jin Xin , Denaux Karen , De Leyn Paul , Van Veer Hans , Depypere Lieven , Jansen Yanina , Pirenne Jacques , Neyrinck Arne , Bouneb Sofian , Ingels Catherine , Jacobs Bart , Godinas Laurent , De Sadeleer Laurens , Vos Robin , Svorcova Monika , Vajter Jaromir , Kolarik Jan , Tavandzis Janis , Havlin Jan , Ozaniak Strizova Zuzana , Pozniak Jiri , Simonek Jan , Vachtenheim Jiri , Lischke Robert , Ceulemans Laurens J. 
Published: June 2024

IntroductionCompared with traditional static ice storage, controlled hypothermic storage (CHS) at 4–10°C may attenuate cold-induced lung injury between procurement and implantation. In this study, we describe the first European lung transplant (LTx) experience with a portable CHS device.MethodsA prospective observational study was conducted of all consecutively performed LTx following CHS (11 November 2022 and 31 January 2024) at two European high-volume centers. The LUNGguard device was used for CHS. The preservation details, total ischemic time, and early postoperative outcomes are described. The data are presented as median (range: minimum–maximum) values.ResultsA total of 36 patients underwent LTx (i.e., 33 bilateral, 2 single LTx, and 1 lobar). The median age was 61 (15–68) years; 58% of the patients were male; 28% of the transplantations had high-urgency status; and 22% were indicated as donation after circulatory death. In 47% of the patients, extracorporeal membrane oxygenation (ECMO) was used for perioperative support. The indications for using the CHS device were overnight bridging (n = 26), remote procurement (n = 4), rescue allocation (n = 2), logistics (n = 2), feasibility (n = 1), and extended-criteria donor (n = 1). The CHS temperature was 6.5°C (3.7°C–9.3°C). The preservation times were 11 h 18 (2 h 42–17 h 9) and 13 h 40 (4 h 5–19 h 36) for the first and second implanted lungs, respectively, whereas the total ischemic times were 13 h 38 (4 h 51–19 h 44) and 15 h 41 (5 h 54–22 h 48), respectively. The primary graft dysfunction grade 3 (PGD3) incidence rates were 33.3% within 72 h and 2.8% at 72 h. Intensive care unit stay was 8 (4–62) days, and the hospital stay was 28 (13–87) days. At the last follow-up [139 (7–446) days], three patients were still hospitalized. One patient died on postoperative day 7 due to ECMO failure. In-hospital Clavien–Dindo complications of 3b were observed in six (17%) patients, and 4a in seven (19%).ConclusionCHS seems safe and feasible despite the high-risk recipient and donor profiles, as well as extended preservation times. PGD3 at 72 h was observed in 2.8% of the patients. This technology could postpone LTx to daytime working hours. Larger cohorts and longer-term outcomes are required to confirm these observations.
Long-term organic farming impact on soil nutrient status and grain yield at the foothill of Himalayas
Authors: Singh Pranjali , Suyal Deep Chandra , Kumar Saurabh , Singh Dhananjay Kumar , Goel Reeta 
Published: June 2024

This study aimed to document the effects of the long-term organic farming (OF) on soil quality, agronomical parameters, crop productivity, and food grain yield compared to the conventional farming (CF) system. The crop used in this study is chickpea (Cicer arietinum), and the field was located at Pantnagar, India, in the foothills of Himalayas. The organic farming approach involved utilizing a blend of farmyard manure and vermicompost, combined with a biopesticide comprising neem oil and cow urine. Chickpea grain micronutrient analysis was done via atomic absorption spectrophotometry. It was found that the physicochemical properties of soil in the organic plot were improved compared to the conventional counterpart. At the post-harvesting stage, the organically managed field had higher soil organic carbon than the conventional field (OF-0.93± 0.05%, CF-0.75 ± 0.12%), higher available nitrogen (OF-317 ± 11 kg/ha, CF-240 ± 22 kg/ha), and more available phosphorus (OF-37.4 ± 1.3 kg/ha, CF-25.2 ± 2.5 kg/ha). The agronomical parameters of the chickpea crop were better under organic cultivation, with a significantly high nodule number, nodule dry weight, and grains per pod. Hence, the grain yield of the crop was better under organic cultivation, with the yield of 1,048 kg ha−1, whereas it was 896.5 kg ha−1 for conventional cultivation. The Fe and Zn contents of organically produced chickpea grains were almost double of their conventional counterpart. Therefore, organic cultivation led to better soil fertility, chickpea grain yield, and nutrient status of the crop. It will be beneficial for the nutritious and sustainable production of chickpeas in Himalayan regions.
The disruptive effects of COPD exacerbation-associated factors on epithelial repair responses
Authors: Kortekaas Rosa K. , Geillinger-Kästle Kerstin E. , Fuentes-Mateos Rocío , van Orsoy Roël , Al-Alyan Nakaa , Burgess Janette K. , Gosens Reinoud 
Published: June 2024

IntroductionExacerbations of chronic obstructive pulmonary disease (COPD) increase mortality risk and can lead to accelerated loss of lung function. The increased inflammatory response during exacerbations contributes to worsening of airflow limitation, but whether it also impacts epithelial repair is unclear. Therefore, we studied the effect of the soluble factor micro-environment during COPD exacerbations on epithelial repair using an exacerbation cocktail (EC), composed of four factors that are increased in COPD lungs during exacerbations (IL-1β, IL-6, IL-8, TNF-α).MethodsMouse organoids (primary CD31-CD45-Epcam+ cells co-cultured with CCL206 fibroblasts) were used to study epithelial progenitor behavior. Mature epithelial cell responses were evaluated using mouse precision cut lung slices (PCLS). The expression of epithelial supportive factors was assessed in CCL206 fibroblasts and primary human lung fibroblasts. ResultsEC exposure increased the number and size of organoids formed, and upregulated Lamp3, Muc5ac and Muc5b expression in day 14 organoids. In PCLS, EC imparted no effect on epithelial marker expression. Pre-treatment of CCL206 fibroblasts with EC was sufficient to increase organoid formation. Additionally, the expression of Il33, Tgfa and Areg was increased in CCL206 fibroblasts from EC treated organoids, but these factors individually did not affect organoid formation or size. However, TGF-α downregulated Foxj1 expression and upregulated Aqp5 expression in day 14 organoids. ConclusionsEC exposure stimulates organoid formation and growth, but it alters epithelial differentiation. EC changes the epithelial progenitor support function of fibroblasts which contributes to observed effects on epithelial progenitors.
Towards a survival risk prediction model for metastatic NSCLC patients on durvalumab using whole-lung CT radiomics
Authors: Patwardhan Kedar A. , RaviPrakash Harish , Nikolaou Nikolaos , Gonzalez-García Ignacio , Salazar José Domingo , Metcalfe Paul , Reischl Joachim 
Published: June 2024

BackgroundExisting criteria for predicting patient survival from immunotherapy are primarily centered on the PD-L1 status of patients. We tested the hypothesis that noninvasively captured baseline whole-lung radiomics features from CT images, baseline clinical parameters, combined with advanced machine learning approaches, can help to build models of patient survival that compare favorably with PD-L1 status for predicting ‘less-than-median-survival risk’ in the metastatic NSCLC setting for patients on durvalumab. With a total of 1062 patients, inclusive of model training and validation, this is the largest such study yet.MethodsTo ensure a sufficient sample size, we combined data from treatment arms of three metastatic NSCLC studies. About 80% of this data was used for model training, and the remainder was held-out for validation. We first trained two independent models; Model-C trained to predict survival using clinical data; and Model-R trained to predict survival using whole-lung radiomics features. Finally, we created Model-C+R which leveraged both clinical and radiomics features.ResultsThe classification accuracy (for median survival) of Model-C, Model-R, and Model-C+R was 63%, 55%, and 68% respectively. Sensitivity analysis of survival prediction across different training and validation cohorts showed concordance indices ([95 percentile]) of 0.64 ([0.63, 0.65]), 0.60 ([0.59, 0.60]), and 0.66 ([0.65,0.67]), respectively. We additionally evaluated generalization of these models on a comparable cohort of 144 patients from an independent study, demonstrating classification accuracies of 65%, 62%, and 72% respectively.ConclusionMachine Learning models combining baseline whole-lung CT radiomic and clinical features may be a useful tool for patient selection in immunotherapy. Further validation through prospective studies is needed.
A two-years real-word study with fingolimod: early predictors of efficacy and an association between EBNA-1 IgG titers and multiple sclerosis progression
Authors: Dominguez-Mozo Maria Inmaculada , Galán Victoria , Ramió-Torrentà Lluís , Quiroga Ana , Quintana E. , Villar Luisa María , Costa-Frossard Lucienne , Fernández-Velasco José Ignacio , Villarrubia Noelia , Garcia-Martinez María Angel , Arroyo Rafael , Alvarez-Lafuente Roberto 
Published: June 2024

BackgroundAlthough fingolimod, a sphingosine 1-phosphate receptor agonist, has shown to be an effective treatment reducing relapse rate and also slowing down the disability progression in relapsing-remitting multiple sclerosis (RRMS) patients, it is important to quickly identify those suboptimal responders.ObjectiveThe main objective was to assess different clinical, radiological, genetic and environmental factors as possible early predictors of response in MS patients treated with fingolimod for 24 months. The secondary objective was to analyze the possible contribution of the environmental factors analyzed to the progression and activity of the disease along the 2-years of follow-up.MethodsA retrospective study with 151 patients diagnosed with MS, under fingolimod treatment for 24 months, with serum samples at initiation and six months later, and with clinical and radiological data at initiation and 24 months later, were included in the study. Clinical and radiological variables were collected to establish NEDA-3 (no evidence of disease activity: patients without relapses, disability progression and new T2 lesions or Gd+ lesions) and EDA (evidence of disease activity: patients with relapses and/or progression and/or new T2 lesions or gadolinium-positive [Gd+] lesions) conditions. Human leukocyte antigen II (HLA-II), EBNA-1 IgG and VCA IgG from Epstein-Barr virus (EBV) and antibody titers against Human herpesvirus 6A/B (HHV-6A/B) were also analyzed.ResultsA total of 151 MS patients fulfilled the inclusion criteria: 27.8% was NEDA-3 (37.5% among those previously treated with high efficacy therapies &gt;24 months). The following early predictors were statistically significantly associated with NEDA-3 condition: sex (male; p=0.002), age at baseline (older; p=0.009), relapses 2-years before fingolimod initiation ≤1 (p=0.010), and absence of Gd+ lesions at baseline (p=0.006). Regarding the possible contribution of the environmental factors included in the study to the activity or the progression of the disease, we only found that EBNA-1 IgG titers decreased in 20.0% of PIRA (progression independent from relapse activity) patients vs. 73.3% of RAW (relapse-associated worsening) patients (p=0.006; O.R. = 11.0).ConclusionMS patients that are male, older, and with a low clinical and radiological activity at fingolimod initiation have a greater probability to reach NEDA-3 condition after two years with this therapy. An intriguing association of EBV with the progression of the disease has also been described, but it should be further study in a larger cohort to confirm these results.
Insufficient PD-1 expression during active autoimmune responses: a deep single-cell proteomics analysis in inflammatory arthritis
Authors: Vetsika Eleni-Kyriaki , Fragoulis George E. , Kyriakidi Maria , Verrou Kleio-Maria , Tektonidou Maria G. , Alissafi Themis , Sfikakis Petros P. 
Published: June 2024

ObjectivesProgrammed cell death protein-1 (PD-1) maintains peripheral immune tolerance by preventing T cell continuous activation. Aiming to understand the extent of PD-1 expression in inflammatory arthritis beyond its involvement with T cells, we assess its presence on various circulating single cells.MethodsMass cytometry analysis of patients with active seropositive/seronegative rheumatoid (RA; n=9/8) and psoriatic (PsA; n=9) arthritis versus healthy controls (HC; n=13), re-evaluating patients after 3 months of anti-rheumatic treatment.ResultsPD-1 was expressed in all leukocyte subpopulations, with the highest PD-1+ cell frequencies in eosinophils (59-73%) and T cells (50–60%), and the lowest in natural-killer cells (1–3%). PD-1+ cell frequencies and PD-1 median expression were comparable between patient subgroups and HC, in the majority of cell subsets. Exceptions included increases in certain T cell/B cell subsets of seropositive RA and specific monocyte subsets and dendritic cells of PsA; an expanded PD-1+CD4+CD45RA+CD27+CD28+ T subset, denoting exhausted T cells, was common across patient subgroups. Strikingly, significant inverse correlations between individual biomarkers of systemic inflammation (ESR and/or serum CRP) and PD-1+ cell frequencies and/or median expression were evident in several innate and adaptive immunity cell subsets of RA and PsA patients. Furthermore, all inverse correlations noted in individuals with active arthritis were no longer discernible in those who attained remission/low disease activity post-treatment.ConclusionPD-1 expression may be insufficient, relative to the magnitude of the concomitant systemic inflammatory response on distinct leukocyte subsets, varying between RA and PsA. Our results point to the potential therapeutic benefits of pharmacological PD-1 activation, to rebalance the autoimmune response and reduce inflammation.
From proteome to candidate vaccines: target discovery and molecular dynamics-guided multi-epitope vaccine engineering against kissing bug
Authors: Albaqami Faisal F. , Altharawi Ali , Althurwi Hassan N. , Alharthy Khalid M. 
Published: June 2024

IntroductionTrypanosoma cruzi is a protozoan parasite that causes the tropical ailment known as Chagas disease, which has its origins in South America. Globally, it has a major impact on health and is transported by insect vector that serves as a parasite. Given the scarcity of vaccines and the limited treatment choices, we conducted a comprehensive investigation of core proteomics to explore a potential reverse vaccine candidate with high antigenicity. MethodsTo identify the immunodominant epitopes, T. cruzi core proteomics was initially explored. Consequently, the vaccine sequence was engineered to possess characteristics of non-allergenicity, antigenicity, immunogenicity, and enhanced solubility. After modeling the tertiary structure of the human TLR4 receptor, the binding affinities were assessed employing molecular docking and molecular dynamics simulations (MDS).ResultsDocking of the final vaccine design with TLR4 receptors revealed substantial hydrogen bond interactions. A server-based methodology for immunological simulation was developed to forecast the effectiveness against antibodies (IgM + IgG) and interferons (IFN-g). The MDS analysis revealed notable levels of structural compactness and binding stability with average RMSD of 5.03 Aring;, beta-factor 1.09e+5 Å, Rg is 44.7 Aring; and RMSF of 49.50 Aring;. This is followed by binding free energies calculation. The system stability was compromised by the complexes, as evidenced by their corresponding Gibbs free energies of -54.6 kcal/mol.DiscussionSubtractive proteomics approach was applied to determine the antigenic regions of the T cruzi. Our study utilized computational techniques to identify B- and T-cell epitopes in the T. cruzi core proteome. In current study the developed vaccine candidate exhibits immunodominant features. Our findings suggest that formulating a vaccine targeting the causative agent of Chagas disease should be the initial step in its development.
The comparison of preoxygenation methods before endotracheal intubation: a network meta-analysis of randomized trials
Authors: Zhong Ming , Xia Rong , Zhou Junyu , Zhang Jing , Yi Xia , Yang Anbo 
Published: June 2024

BackgroundPreoxygenation before endotracheal intubation (ETI) maintains asphyxiated oxygenation and reduces the risk of hypoxia-induced adverse events. Previous studies have compared various preoxygenation methods. However, network meta-analyses (NMAs) of the combined comparison of preoxygenation methods is still lacking.MethodsWe searched for studies published in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library. Review Manager version 5.3 was used to evaluate the risk of bias. The primary outcome of this meta-analysis was low oxygen saturation (SpO2) during ETI. The secondary outcomes included SpO2 &lt;80%, SpO2 &lt;90%, and apnea time during ETI. NMA was performed using R 4.1.2 software gemtc packages in RStudio.ResultsA total of 15 randomized controlled trials were included in this study. Regarding the lowest SpO2, the noninvasive ventilation (NIV) with high-flow nasal cannula (HFNC) group performed better than the other groups. For SpO2 &lt;80%, the NIV group (0.8603467) performed better than the HFNC (0.1373533) and conventional oxygen therapy (COT, 0.0023) groups, according to the surface under the cumulative ranking curve results. For SpO2 &lt;90%, the NIV group (0.60932667) performed better than the HFNC (0.37888667) and COT (0.01178667) groups. With regard to apnea time, the HFNC group was superior to the COT group (mean difference: −50.05; 95% confidence interval: −90.01, −10.09; P = 0.01).ConclusionNetwork analysis revealed that NIV for preoxygenation achieved higher SpO2 levels than HFNC and COT and offered a more significant advantage in maintaining patient oxygenation during ETI. Patients experienced a longer apnea time after HFNC preoxygenation. The combination of NIV with HFNC proved to be significantly superior to other methods. Given the scarcity of such studies, further research is needed to evaluate its effectiveness.Systematic review registrationidentifier CRD42022346013
The potential protective role of peripheral immunophenotypes in Alzheimer’s disease: a Mendelian randomization study
Authors: Zuo Chun-yan , Hu Zhengwei , Hao Xiao-yan , Li Meng-jie , Shi Jing-jing , Guo Meng-nan , Ma Dong-rui , Li Shuang-jie , Liang Yuan-yuan , Zhang Chan , Mao Cheng-yuan , Xu Yuming , Shi Chang-he 
Published: June 2024

IntroductionAlzheimer’s disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a paramount role in AD, but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous.MethodsTwo-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Utilizing the genetic associations of 731 immune cell traits as exposures. We adopted the inverse variance weighted method as the primary approach. The Weighted median and MR-Egger regression methods were employed as supplements. Various sensitivity analyses were performed to assess the robustness of the outcomes.ResultsBased on the IVW method, we identified 14 immune cell traits that significantly reduced the risk of AD, of which six demonstrated statistical significance in both IVW and Weighted median methods. Among the seven immune traits, four were related to regulatory T (Treg) cells : (1) CD25++ CD45RA- CD4 not regulatory T cell % T cell (odds ratio (OR) [95% confidence interval (CI)] = 0.96 [0.95, 0.98], adjusted P = 1.17E−02), (2) CD25++ CD45RA- CD4 not regulatory T cell % CD4+ T cell (OR [95% CI] = 0.97 [0.96, 0.99], adjusted P = 3.77E−02), (3) Secreting CD4 regulatory T cell % CD4 regulatory T cell (OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E−03), (4) Activated &amp; secreting CD4 regulatory T cell % CD4 regulatory T cell(OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E−03). In addition, HLA DR++ monocyte % monocyte (OR [95% CI] = 0.93 [0.89, 0.98], adjusted P = 4.87E−02) was associated with monocytes, and HLA DR on myeloid Dendritic Cell (OR [95% CI] = 0.93 [0.89, 0.97], adjusted P = 1.17E−02) was related to dendritic cells (DCs).ConclusionThese findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.