bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction
Authors: Ardissino Maddalena , Nelson Adam J. , Maglietta Giuseppe , Malagoli Tagliazucchi Guidantonio , Disisto Caterina , Celli Patrizia , Ferrario Maurizio , Canosi Umberto , Cernetti Carlo , Negri Francesco , Merlini Piera Angelica , Tubaro Marco , Berzuini Carlo , Manzalini Chiara , Ignone Gianfranco , Campana Carlo , Moschini Luigi , Ponte Elisabetta , Pozzi Roberto , Fetiveau Raffaela , Buratti Silvia , Paraboschi Elvezia Maria , Asselta Rosanna , Botti Andrea , Tuttolomondo Domenico , Barocelli Federico , Bricoli Serena , Biagi Andrea , Bonura Rosario , Moccetti Tiziano , Crocamo Antonio , Benatti Giorgio , Paoli Giorgia , Solinas Emilia , Notarangelo Maria Francesca , Moscarella Elisabetta , Calabrò Paolo , Duga Stefano , Magnani Giulia , Ardissino Diego 
Published: July 2022

ImportanceThere is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure.MethodsA nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1–22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG).ResultsST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p &lt; 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52–0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up.ConclusionsThere are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes.Trial Registration4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.
Supercritical Carbon Dioxide Turbine Design and Arrangement Optimization
Authors: Li Zhenya , Bian Wenjie , Jiang Li , Liu Chuanliang , Shi Jinyuan , Hao Ning 
Published: July 2022

To achieve a supercritical CO2 cycle power generation system, a 25 MW supercritical CO2 turbine rotor and cylinder were designed. Then, two compact arrangement schemes were proposed in this paper for the optimization of a supercritical CO2 turbine rotor. In Scheme 1, the balance piston was arranged in the cooling gas section, which was more conducive to the arrangement of the dry gas seal. In Scheme II, the oil bearing was replaced by the gas bearing, and the dry gas seals at both ends of the turbine were installed outside the gas bearing, which was combined with the cooling gas section. The results suggest that the length of the rotor is reduced by 9% and 17% based on the above two schemes. The compact arrangement of the supercritical CO2 turbine can well reduce the shaft length of the turbine, which is beneficial to the structural design and operation of the supercritical CO2 turbine.
Bone Marrow-Derived Mesenchymal Stromal Cell Therapy in Severe COVID-19: Preliminary Results of a Phase I/II Clinical Trial
Authors: Grégoire Céline , Layios Nathalie , Lambermont Bernard , Lechanteur Chantal , Briquet Alexandra , Bettonville Virginie , Baudoux Etienne , Thys Marie , Dardenne Nadia , Misset Benoît , Beguin Yves 
Published: July 2022

BackgroundTreatment of acute respiratory distress syndrome (ARDS) associated with COronaVIrus Disease-2019 (COVID-19) currently relies on dexamethasone and supportive mechanical ventilation, and remains associated with high mortality. Given their ability to limit inflammation, induce immune cells into a regulatory phenotype and stimulate tissue repair, mesenchymal stromal cells (MSCs) represent a promising therapy for severe and critical COVID-19 disease, which is associated with an uncontrolled immune-mediated inflammatory response.MethodsIn this phase I-II trial, we aimed to evaluate the safety and efficacy of 3 intravenous infusions of bone marrow (BM)-derived MSCs at 3-day intervals in patients with severe COVID-19. All patients also received dexamethasone and standard supportive therapy. Between June 2020 and September 2021, 8 intensive care unit patients requiring supplemental oxygen (high-flow nasal oxygen in 7 patients, invasive mechanical ventilation in 1 patient) were treated with BM-MSCs. We retrospectively compared the outcomes of these MSC-treated patients with those of 24 matched control patients. Groups were compared by paired statistical tests.ResultsMSC infusions were well tolerated, and no adverse effect related to MSC infusions were reported (one patient had an ischemic stroke related to aortic endocarditis). Overall, 3 patients required invasive mechanical ventilation, including one who required extracorporeal membrane oxygenation, but all patients ultimately had a favorable outcome. Survival was significantly higher in the MSC group, both at 28 and 60 days (100% vs 79.2%, p = 0.025 and 100% vs 70.8%, p = 0.0082, respectively), while no significant difference was observed in the need for mechanical ventilation nor in the number of invasive ventilation-free days, high flow nasal oxygenation-free days, oxygen support-free days and ICU-free days. MSC-treated patients also had a significantly lower day-7 D-dimer value compared to control patients (median 821.0 µg/L [IQR 362.0-1305.0] vs 3553 µg/L [IQR 1155.0-6433.5], p = 0.0085).ConclusionsBM-MSC therapy is safe and shows very promising efficacy in severe COVID-19, with a higher survival in our MSC cohort compared to matched control patients. These observations need to be confirmed in a randomized controlled trial designed to demonstrate the efficacy of BM-MSCs in COVID-19 ARDS.Clinical Trial Registration(www.ClinicalTrials.gov), identifier NCT04445454
Changes in Protonation States of In-Pathway Residues can Alter Ligand Binding Pathways Obtained From Spontaneous Binding Molecular Dynamics Simulations
Authors: Girame Helena , Garcia-Borràs Marc , Feixas Ferran 
Published: July 2022

Protein-ligand binding processes often involve changes in protonation states that can be key to recognize and orient the ligand in the binding site. The pathways through which (bio)molecules interplay to attain productively bound complexes are intricate and involve a series of interconnected intermediate and transition states. Molecular dynamics (MD) simulations and enhanced sampling techniques are commonly used to characterize the spontaneous binding of a ligand to its receptor. However, the effect of protonation state changes of in-pathway residues in spontaneous binding MD simulations remained mostly unexplored. Here, we used molecular dynamics simulations to reconstruct the trypsin-benzamidine binding pathway considering different protonation states of His57. This residue is part of the trypsin catalytic triad and is located more than 10 Å away from Asp189, which is responsible for benzamidine binding in the trypsin S1 pocket. Our MD simulations showed that the binding pathways that benzamidine follow to target the S1 binding site are critically dependent on the His57 protonation state. Binding of benzamidine frequently occurs when His57 is protonated in the delta nitrogen while the binding process is significantly less frequent when His57 is positively charged. Constant-pH MD simulations retrieved the equilibrium populations of His57 protonation states at trypsin active pH offering a clearer picture of benzamidine recognition and binding. These results indicate that properly accounting for protonation states of distal residues can be important in spontaneous binding MD simulations.
An Improved Surgical Technique to Increase Neck Width of Elastase-Induced Aneurysm Model in Rabbits: A Prospective Study
Authors: Zhang Yang , He Yu , Tang ChaoJie , Wu YuFan , Gu Yi , Gu BinXian , Chen Li , Gao WenWei , Zhou ZhiGuo , Qi YouKe , Mao FaJiang , Sun YongNing , Wang Wu 
Published: July 2022

BackgroundRabbit elastase-induced aneurysms have widely been used to test various endovascular materials over the past two decades. However, wide-necked aneurysms cannot be stably constructed.ObjectiveThe purpose of the study was to increase the neck width of the elastase-induced aneurysm model in rabbits via an improved surgical technique with two temporary clips.Materials and MethodsFifty-four elastase-induced aneurysms in rabbits were successfully created. Group 1 was (n = 34) composed of cases in which two temporary aneurysm clips were placed closely medially and laterally to the origin of the right common carotid artery (RCCA), respectively. Group 2 (n = 20) included cases in which a single temporary aneurysm clip was placed crossed the origin of RCCA. Digital subtraction angiography (DSA) was performed before and immediately after elastase incubation and 3 weeks later. The diameter of the origin of RCCA before and immediately after elastase incubation and aneurysm sizes of the two groups were measured and compared. Moreover, the correlation analysis was performed between the diameter of the origin of RCCA immediately after elastase incubation and aneurysm neck width.ResultsThe mean aneurysm neck and dome width of group 1 were both significantly larger than that of group 2 (p-value &lt; 0.001 and p-value = 0.005, respectively). Moreover, the proportion of wide-necked aneurysms (neck width ≥4 mm) in group 1 was significantly larger than that in group 2 (p-value = 0.004) and the mean dome to neck ratio (D/N) of group 1 was smaller than that of group 2 (p-value = 0.008). Furthermore, there was a positive correlation between the diameter of the origin of RCCA immediately after elastase incubation and aneurysm neck width.ConclusionThe improved surgical technique with two temporary clips, focusing on the direct contact of elastase with the origin of RCCA, could increase the neck width of elastase-induced aneurysm models in rabbits.
A Remarkable Case of Acute Motor-Sensory Axonal Polyneuropathy (AMSAN) Variant of Guillain Barré Syndrome, in a Diabetic Patient Infected With COVID-19: A Case Report and Review of the Literature
Authors: Ali Sajjad , Karam Alvina , Lalani Aarish , Jawed Sadia , Moin Musfirah , Douba Zain , Ali Murtaza 
Published: July 2022

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease- 2019 (COVID-19), has been a global epidemic in our healthcare system. SARS-CoV-2 primarily affects the respiratory system, but neurological involvement has also been reported, including Guillain–Barré syndrome (GBS) development.Case PresentationA 58-year-old male with known co-morbid hypertension and type 2 diabetes mellitus presented to the emergency room with complaints of worsening shortness of breath, dry cough, and fever for the past 10 days. On day 20 of hospitalization, he developed neurological symptoms after being tested positive for COVID-19. A neuroelectrophysiology study was conducted to evaluate neurological symptoms and suggested that the patient suffers from acute motor-sensory axonal polyneuropathy (AMSAN). CSF analysis showed elevated protein levels that confirmed the diagnosis of GBS. He was subsequently treated with oral prednisolone and IVIG, which improved neurological symptoms.ConclusionEver since the emergence of COVID-19, GBS has surfaced as to its potentially dangerous outcome. Healthcare professionals should be mindful of GBS and should rule it out in anyone having sensory symptoms or weakness during or after a COVID-19 infection. Its early detection and treatment can result in improved clinical outcomes.
The Impact of Varying Food Availability on Gene Expression in the Liver: Testing the Match-Mismatch Hypothesis
Authors: Feige-Diller Janina , Herrera-Rivero Marisol , Witten Anika , Stoll Monika , Kaiser Sylvia , Richter S. Helene , Sachser Norbert 
Published: July 2022

BackgroundDuring early phases of life, such as prenatal or early postnatal development and adolescence, an organism's phenotype can be shaped by the environmental conditions it experiences. According to the Match-Mismatch hypothesis (MMH), changes to this environment during later life stages can result in a mismatch between the individual's adaptations and the prevailing environmental conditions. Thus, negative consequences in welfare and health can occur. We aimed to test the MMH in the context of food availability, assuming adolescence as a sensitive period of adaptation.MethodsWe have previously reported a study of the physiological and behavioral effects of match and mismatch conditions of high (ad libitum) and low (90% of ad libitum intake) food availability from adolescence to early adulthood in female C57BL/6J mice (n = 62). Here, we performed RNA-sequencing of the livers of a subset of these animals (n = 16) to test the effects of match and mismatch feeding conditions on the liver transcriptome.ResultsIn general, we found no effect of the match-mismatch situations. Contrarily, the amount of food available during early adulthood (low vs. high) drove the differences we observed in final body weight and gene expression in the liver, regardless of the amount of food available to the animals during adolescence. Many of the differentially expressed genes and the corresponding biological processes found to be overrepresented overlapped, implicating common changes in various domains. These included metabolism, homeostasis, cellular responses to diverse stimuli, transport of bile acids and other molecules, cell differentiation, major urinary proteins, and immunity and inflammation.ConclusionsOur previous and present observations found no support for the MMH in the context of low vs high food availability from adolescence to early adulthood in female C57BL/6J mice. However, even small differences of approximately 10% in food availability during early adulthood resulted in physiological and molecular changes with potential beneficial implications for metabolic diseases.
Exome Sequencing Reveals Genetic Variability and Identifies Chronic Prognostic Loci in Chinese Sarcoidosis Patients
Authors: Zhang Qian , Huang Hui , Zhang Meijun , Fang Chuling , Wang Na , Jing Xiaoyan , Guo Jian , Sun Wei , Yang Xiaoyu , Xu Zuojun 
Published: July 2022

BackgroundSarcoidosis is an inflammatory disease characterized by non-caseating granuloma formation in various organs, with several recognized genetic and environmental risk factors. Despite substantial progress, the genetic determinants associated with its prognosis remain largely unknown.ObjectivesThis study aimed to identify the genetic changes involved in sarcoidosis and evaluate their clinical relevance.MethodsWe performed whole-exome sequencing (WES) in 116 sporadic sarcoidosis patients (acute sarcoidosis patients, n=58; chronic sarcoidosis patients, n=58). In addition, 208 healthy controls were selected from 1000 G East Asian population data. To identify genes enriched in sarcoidosis, Fisher exact tests were performed. The identified genes were included for further pathway analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, we used the STRING database to construct a protein network of rare variants and Cytoscape to identify hub genes of signaling pathways.ResultsWES and Fisher’s exact test identified 1,311 variants in 439 protein-coding genes. A total of 135 single nucleotide polymorphisms (SNPs) on 30 protein-coding genes involved in the immunological process based on the GO and KEGG enrichment analysis. Pathway enrichment analysis showed osteoclast differentiation and cytokine–cytokine receptor interactions. Three missense mutations (rs76740888, rs149664918, and rs78251590) in two genes (PRSS3 and CNN2) of immune-related genes showed significantly different mutation frequencies between the disease group and healthy controls. The correlation of genetic abnormalities with clinical outcomes using multivariate analysis of the clinical features and mutation loci showed that the missense variant (rs76740888, Chr9:33796673 G&gt;A) of PRSS3 [p=0.04, odds ratio (OR) = 2.49] was significantly associated with chronic disease prognosis. Additionally, the top two hub genes were CCL4 and CXCR4 based on protein–protein interaction (PPI) network analysis.ConclusionOur study provides new insights into the molecular pathogenesis of sarcoidosis and identifies novel genetic alterations in this disease, especially PRSS3, which may be promising targets for future therapeutic strategies for chronic sarcoidosis.
Using Period Analysis to Timely Assess and Predict 5-Year Relative Survival for Liver Cancer Patients From Taizhou, Eastern China
Authors: Wang Youqing , Zhang Luyao , Han Fang , Li Runhua , Cheng Yongran , Jiang Xiyi , Wang Liangyou , Chen Jinfei , Ji Jianguang , Zhang Yuhua , Chen Tianhui 
Published: July 2022

IntroductionWhile timely assessment of long-term survival for patients with liver cancer is essential for the evaluation of early detection and screening programs of liver cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for liver cancer patients in eastern China.MethodsPatients diagnosed with liver cancer during 2004–2018 from four cancer registries with high-quality data from Taizhou, eastern China, were included. The period analysis was used to calculate the 5-year relative survival (RS) for overall and the stratification by sex, age at diagnosis, and region. The projected 5-year RS of liver cancer patients during 2019–2023 was also assessed using a model-based period analysis.ResultsThe overall 5-year RS for patients with liver cancer during 2014–2018 reached 32.4%, being 29.3% for men and 36.1% for women. The 5-year RS declined along with aging, decreasing from 38.2% for age &lt;45 years to 18.8% for age &gt;74 years, while the 5-year RS for urban area was higher compared to rural area (36.8% vs. 29.3%). The projected overall 5-year RS of liver cancer patients could reach 41.4% during the upcoming period 2019–2023.ConclusionsWe provided, for first time in China using the period analysis, the most up-to-date 5-year RS for patients with liver cancer from Taizhou, eastern China, and also found that the 5-year RS for liver cancer patients have improved greatly during 2004–2018, which has important implications for the timely evaluation of early detection and screening programs for patients with liver cancer in eastern China.
Patient Derived Organoids Confirm That PI3K/AKT Signalling Is an Escape Pathway for Radioresistance and a Target for Therapy in Rectal Cancer
Authors: Wanigasooriya Kasun , Barros-Silva Joao D. , Tee Louise , El-asrag Mohammed E. , Stodolna Agata , Pickles Oliver J. , Stockton Joanne , Bryer Claire , Hoare Rachel , Whalley Celina M. , Tyler Robert , Sillo Toritseju , Yau Christopher , Ismail Tariq , Beggs Andrew D. 
Published: July 2022

ObjectivesPartial or total resistance to preoperative chemoradiotherapy occurs in more than half of locally advanced rectal cancer patients. Several novel or repurposed drugs have been trialled to improve cancer cell sensitivity to radiotherapy, with limited success. We aimed to understand the mechanisms of resistance to chemoradiotherapy in rectal cancer using patient derived organoid models.DesignTo understand the mechanisms underlying this resistance, we compared the pre-treatment transcriptomes of patient-derived organoids (PDO) with measured radiotherapy sensitivity to identify biological pathways involved in radiation resistance coupled with single cell sequencing, genome wide CRISPR-Cas9 and targeted drug screens.ResultsRNA sequencing enrichment analysis revealed upregulation of PI3K/AKT/mTOR and epithelial mesenchymal transition pathway genes in radioresistant PDOs. Single-cell sequencing of pre &amp; post-irradiation PDOs showed mTORC1 and PI3K/AKT upregulation, which was confirmed by a genome-wide CRSIPR-Cas9 knockout screen using irradiated colorectal cancer (CRC) cell lines. We then tested the efficiency of dual PI3K/mTOR inhibitors in improving cancer cell sensitivity to radiotherapy. After irradiation, significant AKT phosphorylation was detected (p=0.027) which was abrogated with dual PI3K/mTOR inhibitors and lead to significant radiosensitisation of the HCT116 cell line and radiation resistant PDO lines.ConclusionsThe PI3K/AKT/mTOR pathway upregulation contributes to radioresistance and its targeted pharmacological inhibition leads to significant radiosensitisation in CRC organoids, making it a potential target for clinical trials.
Case Report: Diagnosis of Mucopolysaccharidosis Type IVA With Compound Heterozygous Galactosamine-6 Sulfatase Variants and Biopsy of Replaced Femoral Heads
Authors: Ma Yiyang , Peng Hao , Hsiang Fuchou , Fang Haoyu , Du Dajiang , Jiang Chenyi , Wang Yehui , Chen Chun , Zhang Changqing , Gao Yun 
Published: July 2022

IntroductionMucopolysaccharidosis Type IVA (MPS IVA) or Morquio A Syndrome, is a rare metabolic disorder caused by compromised galactosamine-6 sulfatase (GALNS) encoded by GALNS gene (NM_000512.5), leading to keratin sulfate (KS), and chondroitin-6-sulfate accumulation in various organs. We present a 17-year-old woman with progressive bilateral hip pain and radiographic evidence of spondyloepiphyseal dysplasia.MethodsDiagnosis of MPS IVA was made based on whole-exome sequencing (WES) of blood samples collected from the patient and family members, high urinary glycosaminoglycan excretion, supportive clinical manifestations, radiographic examinations, including whole-body X-rays, cervical MRI, and pelvic CT. The patient underwent bilateral total hip arthroplasties sequentially, at a 1-month interval. Femoral heads were preserved for the micro-CT (μCT) analysis and the osteochondral histology examination.ResultsThe patient presented with multiple skeletal deformities, including vertebras and long bone deformities. WES disclosed compound heterozygous variants at exon 11 (c.1156C&gt;T) and exon 12 (c.1288C&gt;G) of the GALNS (NM_000512.5). The μCT analysis revealed significant bone quantity loss and microarchitectural change in both weight-bearing area (WBA) and non-weight-bearing area (NWBA) of the femoral heads, while histological analysis showed structural abnormity of articular cartilage in the WBA of the femoral heads.ConclusionWe have found compound heterozygous variants of GALNS. This is also the first study to report the microarchitectural and histological changes of both subchondral bone and articular cartilage of the femoral head in a patient with MPS IVA.