bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic and prognostic significance of serum angiopoietin-1 and -2 concentrations in patients with pulmonary hypertension
Authors: Enomoto Noriyuki , Suzuki Seiichiro , Hozumi Hironao , Karayama Masato , Suzuki Yuzo , Furuhashi Kazuki , Fujisawa Tomoyuki , Nakamura Yutaro , Odagiri Keiichi , Ishikawa Takamichi , Kataoka Kensuke , Kondoh Yasuhiro , Maekawa Masato , Inui Naoki , Watanabe Hiroshi , Suda Takafumi 
Published: July 2021

AbstractSeveral biomarkers for detecting pulmonary hypertension (PH) have been reported. However, these biomarkers are deemed insufficient to detect PH in its early stages. We evaluated the utility of serum angiopoietin (ANGP), a glycoprotein related to angiogenesis, as a diagnostic and prognostic biomarker of PH. Patients with PH who underwent right-heart catheterization, were retrospectively studied. Serum concentrations of ANGP-1 and ANGP-2 were measured using an enzyme-linked immunosorbent assay in patients with PH (n = 32), those with idiopathic pulmonary fibrosis (IPF) without PH (as a disease control, n = 75), and age-matched healthy controls (HC, n = 60). Nineteen patients (59.4%) with PH had World Health Organization group 3 PH. Serum ANGP-2 concentration, but not ANGP-1, in patients with PH was significantly higher compared with that in HC (p = 0.025) and in patients with IPF without PH (p = 0.008). Serum ANGP-2 concentration in patients with PH positively and significantly correlated with N-terminal pro-B-type natriuretic peptide (r = 0.769, p < 0.001), right ventricular diameter on echocardiography (r = 0.565, p = 0.035), and mean pulmonary arterial pressure (r = 0.449, p = 0.032) and pulmonary vascular resistance (r = 0.451, p = 0.031) on right-heart catheterization. ANGP-1 and ANGP-2 were expressed on lung vascular endothelial cells, as shown by immunohistochemistry. Patients with PH with higher ANGP-2 concentration (≥ 2.48 ng/mL) had significantly worse survival (p = 0.022). Higher ANGP-2 concentration was a significant worse prognostic factor (hazard ratio = 6.063, p = 0.037), while serum ANGP-1 concentration was not. In conclusion, serum ANGP-2 may be a useful diagnostic and prognostic biomarker in patients with PH, especially in patients with group 3 PH.
Exercise training mitigates ER stress and UCP2 deficiency-associated coronary vascular dysfunction in atherosclerosis
Authors: Hong Junyoung , Park Eunkyung , Lee Jonghae , Lee Yang , Rooney Bridgette V. , Park Yoonjung 
Published: July 2021

AbstractEndoplasmic reticulum (ER) stress and uncoupling protein-2 (UCP2) activation are opposing modulators of endothelial dysfunction in atherosclerosis. Exercise reduces atherosclerosis plaques and enhances endothelial function. Our aim was to understand how exercise affects ER stress and UCP2 activation, and how that relates to endothelial dysfunction in an atherosclerotic murine model. Wild type (C57BL/6, WT) and apolipoprotein-E-knockout (ApoEtm1Unc, ApoE KO) mice underwent treadmill exercise training (EX) or remained sedentary for 12 weeks. Acetylcholine (ACh)-induced endothelium-dependent vasodilation was determined in the presence of an eNOS inhibitor (L-NAME), UCP2 inhibitor (genipin), and ER stress inducer (tunicamycin). UCP2, ER stress markers and NLRP3 inflammasome signaling were quantified by western blotting. p67phox and superoxide were visualized using immunofluorescence and DHE staining. Nitric oxide (NO) was measured by nitrate/nitrite assay. ACh-induced vasodilation was attenuated in coronary arterioles of ApoE KO mice but improved in ApoE KO-EX mice. Treatment of coronary arterioles with L-NAME, tunicamycin, and genipin significantly attenuated ACh-induced vasodilation in all mice except for ApoE KO mice. Exercise reduced expression of ER stress proteins, TXNIP/NLRP3 inflammasome signaling cascades, and Bax expression in the heart of ApoE KO-EX mice. Further, exercise diminished superoxide production and NADPH oxidase p67phox expression in coronary arterioles while simultaneously increasing UCP2 expression and nitric oxide (NO) production in the heart of ApoE KO-EX mice. Routine exercise alleviates endothelial dysfunction in atherosclerotic coronary arterioles in an eNOS, UCP2, and ER stress signaling specific manner, and resulting in reduced TXNIP/NLRP3 inflammasome activity and oxidative stress.
Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood
Authors: Latorre-Pellicer Ana , Gil-Salvador Marta , Parenti Ilaria , Lucia-Campos Cristina , Trujillano Laura , Marcos-Alcalde Iñigo , Arnedo María , Ascaso Ángela , Ayerza-Casas Ariadna , Antoñanzas-Pérez Rebeca , Gervasini Cristina , Piccione Maria , Mariani Milena , Weber Axel , Kanber Deniz , Kuechler Alma , Munteanu Martin , Khuller Katharina , Bueno-Lozano Gloria , Puisac Beatriz , Gómez-Puertas Paulino , Selicorni Angelo , Kaiser Frank J. , Ramos Feliciano J. , Pié Juan 
Published: July 2021

AbstractPostzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families.
Non-communicable diseases deaths attributable to high body mass index in Chile
Authors: Riquelme Ricardo , Rezende Leandro F. M. , Guzmán-Habinger Juan , Chávez Javiera L. , Celis-Morales Carlos , Ferreccio Catterina , Ferrari Gerson 
Published: July 2021

AbstractWe estimated the proportion and number of deaths from non-communicable diseases (NCD) attributable to high body mass index (BMI) in Chile in 2018. We used data from 5927 adults from a 2016–2017 Chilean National Health Survey to describe the distribution of BMI. We obtained the number of deaths from NCD from the Ministry of Health. Relative risks (RR) and 95% confidence intervals per 5 units higher BMI for cardiovascular disease, cancer, and respiratory disease were retrieved from the Global BMI Mortality Collaboration meta-analyses. The prevalences of overweight and obesity were 38.9% and 39.1%, respectively. We estimated that reducing population-wide BMI to a theoretical minimum risk exposure level (mean BMI: 22.0 kg/m2; standard deviation: 1) could prevent approximately 21,977 deaths per year (95%CI 13,981–29,928). These deaths represented about 31.6% of major NCD deaths (20.1–43.1) and 20.4% of all deaths (12.9–27.7) that occurred in 2018. Most of these preventable deaths were from cardiovascular diseases (11,474 deaths; 95% CI 7302–15,621), followed by cancer (5597 deaths; 95% CI 3560–7622) and respiratory disease (4906 deaths; 95% CI 3119–6684). A substantial burden of NCD deaths was attributable to high BMI in Chile. Policies and population-wide interventions are needed to reduce the burden of NCD due to high BMI in Chile.
Towards a better understanding of the HTL process of lignin-rich feedstock
Authors: Ciuffi Benedetta , Loppi Massimiliano , Rizzo Andrea Maria , Chiaramonti David , Rosi Luca 
Published: July 2021

AbstractThe hydrothermal liquefaction reactions (HTL) in subcritical conditions of a lignin residue has been studied on a lab scale. The starting material was a lignin rich residue co-produced by an industrial plant situated in Northern Italy producing lignocellulosic bioethanol. The reactions were carried out in batch mode using stainless steel autoclaves. The experiments were under the following operating conditions: two different temperatures (300–350 °C), the presence of basis catalysts (NaOH, and NH4OH) in different concentrations and the presence/absence of capping agent 2,6-bis-(1,1-dimethylethyl)-4-methylphenol (BHT). Lignin residue and reaction products were characterized by analytical and spectroscopic techniques such as CHN-S, TGA, GC–MS, EPR, and 1H-NMR with (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (T.E.M.P.O.). The addition of BHT did not significantly affect the yield of char which is formed by radical way. Spectroscopic analysis indicated that the level of radicals during the reaction was negligible. Therefore, the results obtained experimentally suggest that the reaction takes place via an ionic route while radical species would play a minor role.
Impact on patients with oral squamous cell carcinoma in different anatomical subsites: a single-center study in Taiwan
Authors: Lin Nan-Chin , Hsien Su-I , Hsu Jui-Ting , Chen Michael Y. C. 
Published: July 2021

AbstractThe incidence of oral cavity squamous cell carcinoma (OSCC) is particularly high in South Asia. According to the National Comprehensive Cancer Network, OSCC can arise in several subsites. We investigated survival rates and the clinical and pathological characteristics of OSCC in different anatomical subsites in the Taiwanese population. We retrospectively analyzed data for 3010 patients with OSCC treated at the Changhua Christian Hospital. Subsequently, we compared clinical and pathological features of OSCC in different subsites. Pathological T4 stage OSCCs occurred in the alveolar ridge and retromolar trigone in 56.4% and 43.7% of cases, respectively. More than 25% of patients with tongue OSCC and 23.4% of those with retromolar OSCC had lymph node metastasis. The prognosis was worst for hard palate OSCC (hazard ratio 1.848; p < 0.001) and alveolar ridge OSCC (hazard ratio 1.220; p = 0.017). Retromolar OSCC recurred most often and tongue OSCC second most often. The risk for cancer-related mortality was highest for hard palate OSCC, followed by alveolar ridge and retromolar OSCC. We found distinct differences in survival among the different subsites of OSCC. Our findings may also help prompt future investigations of OSCC in different subsites in Taiwanese patients.
Molecular analysis of Pseudomonas aeruginosa strains isolated from cystic fibrosis patients
Authors: Jarych Dariusz , Augustynowicz-Kopec Ewa , Iwanska Agnieszka , Parniewski Pawel , Majchrzak Marta 
Published: July 2021

AbstractPseudomonas aeruginosa is a severe bacterial pathogen. Due to the genetic flexibility among strains, chronic airways infection can lead to mortality among cystic fibrosis (CF) patients. It is essential to develop patient-specific therapy which will rely on phenotypic and genomic diversity. The primary objective of this study was to assess the genomic variability of P. aeruginosa strains, using two different molecular techniques for tracking the epidemiological transmissions. This study applied a multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) for an efficient genotyping of clinical P. aeruginosa strains isolated from CF patients and compared results with a TRS-PCR typing. The percentage similarity analysis was performed using the categorical multi-state coefficient and UPGMA method. Based on the MLVA and TRS-PCR group assessment, 43 P. aeruginosa strains/variants were detected among the 63 clinical isolates from eight CF patients. The study of P. aeruginosa isolates has revealed that during chronic bacterial infections, CF patients harbor different P. aeruginosa strains or variants within the same host over the years. P. aeruginosa genotypes diversity may result from infection with several strains and result from a microevolution process of an initially acquired strain. The TRS-PCR method proposed in this work can complement the MLVA scheme. It can also be used as a preliminary method for genetic typing of P. aeruginosa isolates in CF patients.
Proteomic study of Desulfovibrio ferrophilus IS5 reveals overexpressed extracellular multi-heme cytochrome associated with severe microbiologically influenced corrosion
Authors: Chatterjee Mohor , Fan Yu , Cao Fang , Jones Aaron A. , Pilloni Giovanni , Zhang Xiaozhou 
Published: July 2021

AbstractMicrobiologically influenced corrosion (MIC) is recognized as a considerable threat to carbon steel asset integrity in the oil and gas industry. There is an immediate need for reliable and broadly applicable methods for detection and monitoring of MIC. Proteins associated with microbial metabolisms involved in MIC could serve as useful biomarkers for MIC diagnosis and monitoring. A proteomic study was conducted using a lithotrophically-grown bacterium Desulfovibrio ferrophilus strain IS5, which is known to cause severe MIC in seawater environments. Unique proteins, which are differentially and uniquely expressed during severe microbial corrosion by strain IS5, were identified. This includes the detection of a multi-heme cytochrome protein possibly involved in extracellular electron transfer in the presence of the carbon steel. Thus, we conclude that this newly identified protein associated closely with severe MIC could be used to generate easy-to-implement immunoassays for reliable detection of microbiological corrosion in the field.
Comparison of cervical muscle isometric force between migraine subgroups or migraine-associated neck pain: a controlled study
Authors: Florencio Lidiane Lima , de Oliveira Anamaria Siriani , Pinheiro Carina Ferreira , Will-Lemos Tenysson , Dach Fabíola , Fernández-de-las-Peñas César , Bevilaqua-Grossi Débora 
Published: July 2021

AbstractThis study aimed to verify if migraine frequency or migraine-associated neck pain were associated with a reduction of normalized force and altered electromyographic activity during maximal cervical muscle isometric contractions. Additionally, it aimed to assess the correlation of normalized isometric force with years with migraine, headache frequency, headache intensity, migraine-related disability, and severity of cutaneous allodynia. The sample comprises 71 women with migraine (40/31 episodic/chronic, 42/18 with/without neck pain) and 32 women without headache. Cervical muscle isometric force in flexion, extension, and lateral flexion was assessed synchronized with the acquisition of superficial electromyography from the cervical muscles. Women with episodic migraine presented lower normalized isometric force in extension, flexion, and right and left lateral flexions than controls (P < 0.05). Women with migraine and neck pain exhibited lower cervical extension and right/left lateral-flexions normalized isometric force than controls (P < 0.05). No significant differences were observed in antagonist activity. Normalized isometric force in all directions showed weak to moderate correlations with the severity of self-reported symptoms of cutaneous allodynia (− 0.25 ≥ r ≥ − 0.39). No additional linear correlation with clinical migraine features was observed. In conclusion, cervical muscle weakness may be associated with episodic migraine and neck pain concurrent with migraine attacks without altered antagonist activity. Additionally, it may also be related to the severity of cutaneous allodynia.
Environmental determinants of the occurrence and activity of Ixodes ricinus ticks and the prevalence of tick-borne diseases in eastern Poland
Authors: Zając Zbigniew , Kulisz Joanna , Bartosik Katarzyna , Woźniak Aneta , Dzierżak Malwina , Khan Adil 
Published: July 2021

AbstractIxodes ricinus is the most widely distributed tick species in Europe. Mainly deciduous and mixed forests, pastures, and urban parks are habitats preferred by this species. I. ricinus ticks are also one of the most important reservoirs and vectors of human and animal infectious diseases on the continent. Borrelia burgdorferi s.l. spirochetes causing Lyme borreliosis (LB) in humans and tick borne encephalitis virus (TBEV), which is a causative agent of tick-borne encephalitis (TBE), are pathogens with the highest medical importance transmitted by this species. Investigations of the environmental determinants of the occurrence and activity of I. ricinus are crucial for elucidation of the environmental background of tick-borne diseases. In eastern Poland, I. ricinus is a common species with peak activity recorded in May in the entire region. During this period, 49 females, 32 males, and 55 I. ricinus nymphs were collected from an area of 900 m2. The results of the present study show that the occurrence and seasonal activity of this tick species are mainly influenced by microhabitat conditions, and saturation deficit has a significant effect on the activity of the species. Eastern Poland is characterized by a high incidence of LB and TBE. We have shown a correlation between the forest cover and the number of reported cases of tick-borne diseases.
Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action
Authors: Palte Rachel L. , Juan Veronica , Gomez-Llorente Yacob , Bailly Marc Andre , Chakravarthy Kalyan , Chen Xun , Cipriano Daniel , Fayad Ghassan N. , Fayadat-Dilman Laurence , Gathiaka Symon , Greb Heiko , Hall Brian , Handa Mas , Hsieh Mark , Kofman Esther , Lin Heping , Miller J. Richard , Nguyen Nhung , O’Neil Jennifer , Shaheen Hussam , Sterner Eric , Strickland Corey , Sun Angie , Taremi Shane , Scapin Giovanna 
Published: July 2021

AbstractHuman Arginase 1 (hArg1) is a metalloenzyme that catalyzes the hydrolysis of l-arginine to l-ornithine and urea, and modulates T-cell-mediated immune response. Arginase-targeted therapies have been pursued across several disease areas including immunology, oncology, nervous system dysfunction, and cardiovascular dysfunction and diseases. Currently, all published hArg1 inhibitors are small molecules usually less than 350 Da in size. Here we report the cryo-electron microscopy structures of potent and inhibitory anti-hArg antibodies bound to hArg1 which form distinct macromolecular complexes that are greater than 650 kDa. With local resolutions of 3.5 Å or better we unambiguously mapped epitopes and paratopes for all five antibodies and determined that the antibodies act through orthosteric and allosteric mechanisms. These hArg1:antibody complexes present an alternative mechanism to inhibit hArg1 activity and highlight the ability to utilize antibodies as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.
PRL3 induces polyploid giant cancer cells eliminated by PRL3-zumab to reduce tumor relapse
Authors: Thura Min , Ye Zu , Al-Aidaroos Abdul Qader , Xiong Qiancheng , Ong Jun Yi , Gupta Abhishek , Li Jie , Guo Ke , Ang Koon Hwee , Zeng Qi 
Published: July 2021

AbstractPRL3, a unique oncotarget, is specifically overexpressed in 80.6% of cancers. In 2003, we reported that PRL3 promotes cell migration, invasion, and metastasis. Herein, firstly, we show that PRL3 induces Polyploid Giant Cancer Cells (PGCCs) formation. PGCCs constitute stem cell-like pools to facilitate cell survival, chemo-resistance, and tumor relapse. The correlations between PRL3 overexpression and PGCCs attributes raised possibilities that PRL3 could be involved in PGCCs formation. Secondly, we show that PRL3+PGCCs co-express the embryonic stem cell markers SOX2 and OCT4 and arise mainly due to incomplete cytokinesis despite extensive DNA damage. Thirdly, we reveal that PRL3+PGCCs tolerate prolonged chemotherapy-induced genotoxic stress via suppression of the pro-apoptotic ATM DNA damage-signaling pathway. Fourthly, we demonstrated PRL3-zumab, a First-in-Class humanized antibody drug against PRL3 oncotarget, could reduce tumor relapse in ‘tumor removal’ animal model. Finally, we confirmed that PGCCs were enriched in relapse tumors versus primary tumors. PRL3-zumab has been approved for Phase 2 clinical trials in Singapore, US, and China to block all solid tumors. This study further showed PRL3-zumab could potentially serve an ‘Adjuvant Immunotherapy’ after tumor removal surgery to eliminate PRL3+PGCC stem-like cells, preventing metastasis and relapse.
Rational engineering of ratiometric calcium sensors with bright green and red fluorescent proteins
Authors: Zhang Diming , Redington Emily , Gong Yiyang 
Published: July 2021

AbstractRatiometric genetically encoded calcium indicators (GECIs) record neural activity with high brightness while mitigating motion-induced artifacts. Recently developed ratiometric GECIs primarily employ cyan and yellow-fluorescent fluorescence resonance energy transfer pairs, and thus fall short in some applications that require deep tissue penetration and resistance to photobleaching. We engineered a set of green-red ratiometric calcium sensors that fused two fluorescent proteins and calcium sensing domain within an alternate configuration. The best performing elements of this palette of sensors, Twitch-GR and Twitch-NR, inherited the superior photophysical properties of their constituent fluorescent proteins. These properties enabled our sensors to outperform existing ratiometric calcium sensors in brightness and photobleaching metrics. In turn, the shot-noise limited signal fidelity of our sensors when reporting action potentials in cultured neurons and in the awake behaving mice was higher than the fidelity of existing sensors. Our sensor enabled a regime of imaging that simultaneously captured neural structure and function down to the deep layers of the mouse cortex.
Improving personalized tumor growth predictions using a Bayesian combination of mechanistic modeling and machine learning
Authors: Mascheroni Pietro , Savvopoulos Symeon , Alfonso Juan Carlos López , Meyer-Hermann Michael , Hatzikirou Haralampos 
Published: July 2021

AbstractBackgroundIn clinical practice, a plethora of medical examinations are conducted to assess the state of a patient’s pathology producing a variety of clinical data. However, investigation of these data faces two major challenges. Firstly, we lack the knowledge of the mechanisms involved in regulating these data variables, and secondly, data collection is sparse in time since it relies on patient’s clinical presentation. The former limits the predictive accuracy of clinical outcomes for any mechanistic model. The latter restrains any machine learning algorithm to accurately infer the corresponding disease dynamics.MethodsHere, we propose a novel method, based on the Bayesian coupling of mathematical modeling and machine learning, aiming at improving individualized predictions by addressing the aforementioned challenges.ResultsWe evaluate the proposed method on a synthetic dataset for brain tumor growth and analyze its performance in predicting two relevant clinical outputs. The method results in improved predictions in almost all simulated patients, especially for those with a late clinical presentation (>95% patients show improvements compared to standard mathematical modeling). In addition, we test the methodology in two additional settings dealing with real patient cohorts. In both cases, namely cancer growth in chronic lymphocytic leukemia and ovarian cancer, predictions show excellent agreement with reported clinical outcomes (around 60% reduction of mean squared error).ConclusionsWe show that the combination of machine learning and mathematical modeling approaches can lead to accurate predictions of clinical outputs in the context of data sparsity and limited knowledge of disease mechanisms.