bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial changes in healthy mice retina in an early aging stage
Authors: Fernández‐Albarral José A. , Salobrar‐Garcia Elena , López‐Cuenca Inés , Rojas Lozano María Pilar , José Salazar Corral Juan , De Hoz Rosa , Aviles‐Trigueros Marcelino , Vidal‐Sanz Manuel , Ramirez Jose Manuel , Ramírez Ana I. 
Published: January 2021

AbstractPurposeTo quantify different morphological signs of microglial cells activation, as well as to analyze the P2RY12, MHC‐II and CD68 expression in 15‐month old mice , an early stage of aging (aged naïve) in comparison with a young adult mice (young naïve).MethodsYoung naïve (n = 6) and aged naïve (n = 6) mice were analyzed. Retinal whole‐mounts were immunolabeled with: 1) anti Iba‐1 to quantify: i) Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); ii) area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ ganglion cell layer (NFL‐GCL) iii) cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; iv) arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL; number of vertical processes of Iba‐1+ cells (VPIbac) beetween the OS and OPL. 2) anti‐P2RY12 to identify resident microglia, anti‐CD68 and anti‐MHC‐II as a microglial activation marker.ResultsIn aged naïve with respect to young naïve the quantitative analysis showed: i) a non‐significant increase in the Ibacn in OS; ii) a non‐significant decrease in the AAIbac in OPL; iii) a significant increase in the CbIbac in OPL, IPL and NFL‐GCL and iv) a significant increase in the VPIbac. When we analyzed the expression of P2RY12, CD68 and MHC‐II we observed: i) in young naïve all Iba‐1+ cells were P2RY12+, except perivascular and dendritic cells, but in the aged naïve some cells were Iba‐1+/P2RY12‐; ii) in aged naïve numerous amoeboid‐like CD68+ cells were found while in the young naïve the expression of CD68 practically was absent, and iii) in both young naïve and aged naïve no expression of MHC‐II was observed.ConclusionsIn 15‐month‐old mice, morphological changes and in the expression of P2RY12, CD68 and MHC‐II occurs in the microglial cells compared to young adult mice. These signs show a non‐pathological state of microglial activation that could influence of retinal age‐related disorders.
Long‐term Graft Survival and Visual Outcome of Deep Anterior lamellar keratoplasty versus penetrating keratoplasty for keratoconus: A minimum of 10 years follow‐up
Authors: Almazyad Enmar , Alosaily Abdullah , Ahmad Abeer , Al‐Swailem Samar 
Published: January 2021

AbstractPurposeTo compare long‐term visual outcome and graft survival between Deep Anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) for keratoconus (KC), with a minimum of ten years follow‐up.MethodsRetrospective, comparative cohort study of 191 KC eyes who underwent DALK and PK between January 2000 and October 2006, at a largest tertiary eye hospital in the country. Baseline and postoperative outcomes included: best‐corrected visual acuity (BCVA), spherical equivalent (SE), keratometric power, and keratometric astigmatism. Difference in overall effect and effect at each time point were presented. Graft survival was analyzed with use of the Kaplan ‐Meier survival method.Results97 (50.8%) eyes underwent PK and 94 (49.2%) eyes underwent DALK. mean follow‐up in PK & DALK groups were 13.45±2.7 years and 12.18±1.9 years, respectively. Post‐operative Mean BCVA (LogMar) was significantly worse in DALK (0.49 ± 0.26) in comparison to PK (0.40 ± 0.2) at 3 months whereas BCVA was significantly better in DALK (0.23 ± 0.18) in comparison to PK (0.37 ± 0.63) at the last follow‐up. However, the overall effect of BCVA for both groups was insignificant. The overall effect of SE and keratometric power were insignificant. More complications were reported in PK (69%) group versus DALK (31%). At last follow‐up, 15 grafts failed, 9 were PK and 6 were DALK. Graft rejection was the most common reported cause of failure in both groups (PK 73%, DALK 50%). There was no overall significant difference between PK and DALK in time to graft failure (p = 0.59).ConclusionsLong‐term follow‐up of PK and DALK for KC showed similar overall graft survival and no significant difference in mean BCVA overall effect, indicating that both keratoplasties can offer long‐term satisfactory visual outcomes with less rejection and less overall post‐operative complications in DALK.
Causes of low vision in a Greek population
Authors: Almpanidou Stavroula , Almaliotis Diamantis , Karamitopoulos Leonidas , Topouzis Fotios , Labiris Georgios , Karampatakis Vasileios 
Published: January 2021

PurposeLow vision (LV) is one of the major causes affecting detrimentally the quality of life of individuals. There are various underlying ocular pathologies resulting in LV. The purpose of this study is to determine the prevalence of the main causes of low vision in a population attended a university outpatient unit in Greece.MethodsThe records of all patients within a timeframe of about 18 months period were retrospectively reviewed. In this study, individuals with best‐corrected visual acuity (BCVA) of 3/60 to <6/18 were characterized as having LV, according to the World Health Organization (WHO) definition of LV.ResultsTwo hundred thirty‐six LV patients were included—114 (48.3%) were males and 122 (51.7%) females. The age of patients ranged from ten to ninety‐nine, with a mean age of 70.9 ± 18.9 years. BCVA ranged from 1.32 logMAR to 0.33 logMAR, with a mean VA of 0.7152 ± 0.3146 logMAR in the better eye. The distribution of LV causes in this population was the following: Age‐related macular degeneration (AMD) accounting for 50.0% of the cases (118/236), diabetic retinopathy (DR) 19.9% (47/236) and glaucoma 7.2% (17/236). Other causes of LV included retinitis pigmentosa in a percentage of 5.3% and other hereditary retinal diseases (3%), previous retinal detachment (2.5%), other maculopathies (2.1%) and various other ocular diseases (9.7%). Out of 118 patients with AMD, 75 (64.1%) had the dry form and 42 (35.9%) had the wet form of the disease and among patients with diabetic retinopathy as underlying cause of LV, 31 (68.9%) had the proliferative and 14 (31.1%) had the non‐proliferative form of the disease.ConclusionsAge‐related macular degeneration, diabetic retinopathy and glaucoma constituted the three main causes of low vision in the study population, followed by other ocular diseases.
Italian expert‐based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e‐Delphi consensus
Authors: Grandi Vieri , Baldo Antonello , Berti Emilio , Quaglino Pietro , Rupoli Serena , Alaibac Mauro , Alberti‐Violetti Silvia , Amerio Paolo , Brazzelli Valeria , Bruni Pier Luigi , Calzavara‐Pinton Piergiacomo , Parodi Aurora , Cozzani Emanuele , Burlando Martina , Fargnoli Maria Concetta , Gambini Daniele , Iacovelli Paolo , Pacifico Alessia , Longo Caterina , Monfrecola Giuseppe , Motolese Alberico , Mozzicafreddo Giorgio , Cota Carlo , Pigatto Paolo , Pileri Alessandro , Savoia Paola , Simonacci Marco , Venturini Marina , Offidani Annamaria , Molinelli Elisa , Pellegrino Michele , Trovato Emanuele , Piccinno Roberta , Lawrence Karl , Pimpinelli Nicola 
Published: January 2021

AbstractBackgroundPhototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule.AimsThe primary aim of this study was to establish the first structured, expert‐based consensus regarding the indications and technical schedules of NB‐UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item.Materials & MethodsE‐delphi study. Item‐specific expert consensus was defined as the number of “Totally Agree” results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic.ResultsOverall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7).ConclusionsItems related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB‐UVB and PUVA in MF.
A long‐term in vitro culture of bovine epithelial cells on collagen rafts
Authors: Peña‐Zanoni Milagros , García Daniela Celeste , Roldán‐Olarte Mariela , Valdecantos Pablo Alberto 
Published: January 2021

AbstractIn the present work, we established and characterized a 3D functional polarized primary bovine oviduct epithelial cells (BOECs) culture on free‐floating type I collagen hydrogels (rafts) at an air‐liquid interface (ALI). Intercellular junctions, ultrastructural cellular morphology and the expression of the OVGP1 closely recapitulated those of the in vivo epithelium lining. These morphological and physiological epithelial cell features were maintained under standard DMEM/F12 with 10% foetal bovine serum culture medium for at least 28 days of ALI culture. The versatility of the BOECs raft cultures should allow testing of toxicity compounds, in vitro evaluation of physiological or pathological oviductal states, and the study of epithelial‐mesenchymal interactions that are critical for the maintenance of oviductal homeostasis.
Modeling of a Fractional Order Element Based on Bacterial Cellulose and Ionic Liquids
Authors: Caponetto R. , Graziani S. , Murgano E. , Trigona C. , Pollicino A. , Di Pasquale G. 
Published: January 2021

Abstract
In this paper, a novel fractional-order element (FOE) is modeled in a wide frequency range. The FOE is based on a green biopolymer, i.e., bacterial cellulose (BC), infused with ionic liquids (ILs). The modeling is performed in the frequency domain and a lumped-circuit model is proposed. The model is an evolution with respect to a simpler one already introduced by the authors, for a narrower frequency range. Results show that ILs generate a quite complex frequency domain behavior, which can be described in the framework of FOEs. Furthermore, results on the time stability of the device under investigation are given.
Association between hemoglobin A1c variability and hypoglycemia-related hospitalizations in veterans with diabetes mellitus
Authors: Zhao Molly J Y , Prentice Julia C , Mohr David C , Conlin Paul R 
Published: January 2021

IntroductionTo study the impact of hemoglobin A1c (A1c) variability on the risk of hypoglycemia-related hospitalization (HRH) in veterans with diabetes mellitus.Research design and methods342 059 veterans with diabetes aged 65 years or older were identified for a retrospective cohort study. All participants had a 3-year baseline period from January 1, 2005 to December 31, 2016, during which they had at least four A1c tests. A1c variability measures included coefficient of variation (A1c CV), A1c SD, and adjusted A1c SD. HRH was identified during a 2-year follow-up period from Medicare and the Veterans Health Administration through validated algorithms of International Classification of Diseases (ICD)-9 and ICD-10 codes. Logistic regression modeling was used to evaluate the relationship between A1c variability and HRH risk while controlling for relevant clinical covariates.Results2871 patients had one or more HRH in the 2-year follow-up period. HRH risk increased with greater A1c variability, and this was consistent across A1c CV, A1c SD, and adjusted A1c SD. Average A1c levels were also independently associated with HRH, with levels <7.0% (53 mmol/mol) having lower risk and >9% (75 mmol/mol) with greater risk. The relationships between A1c variability remained significant after controlling for average A1c levels and prior HRH during the baseline period.ConclusionIncreasing A1c variability and elevated A1c levels are associated with a greater risk of HRH in older adults with diabetes. Clinicians should consider A1c variability when assessing patients for risk of severe hypoglycemia.
Outcome of patients with prior coronary bypass surgery admitted with an acute coronary syndrome
Authors: Marcuschamer Ilan , Zusman Oren , Iakobishvili Z , Assali Abid R , Vaknin-Assa Hanah , Goldenberg Ilan , Cohen Tal , Shlomo Nir , Kornowski Ran , Eisen Alon 
Published: January 2021

BackgroundPatients with prior coronary artery bypass graft surgery (CABG) are at increased risk for recurrent cardiovascular ischaemic events. Advances in management have improved prognosis of patients with acute coronary syndrome (ACS), yet it is not known whether similar trends exist in patients with prior CABG.AimExamine temporal trends in the prevalence, treatment and clinical outcomes of patients with prior CABG admitted with ACS.MethodsTime-dependent analysis of patients with or without prior CABG admitted with an ACS who enrolled in the ACS Israeli Surveys between 2000 and 2016. Surveys were divided into early (2000–2008) and late (2010–2016) time periods. Outcomes included 30 days major adverse cardiac events (30d MACE) (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularisation) and 1-year mortality.ResultsAmong 15 152 patients with ACS, 1506 (9.9%) had a prior CABG. Patients with prior CABG were older (69 vs 63 years), had more comorbidities and presented more with non-ST elevation-ACS (82% vs 51%). Between time periods, utilisation of antiplatelets, statins and percutaneous interventions significantly increased in both groups (p<0.001 for each). The rate of 30d MACE decreased in patients with (19.1%–12.4%, p=0.001) and without (17.4%–9.5%, p<0.001) prior CABG. However, 1-year mortality decreased only in patients without prior CABG (10.5% vs 7.4%, p<0.001) and remained unchanged in patients with prior CABG. Results were consistent after propensity matching.ConclusionsDespite an improvement in the management and prognosis of patients with ACS in the last decade, the rate of 1-year mortality of patients with prior CABG admitted with an ACS remained unchanged.
Deletion of Cbl-b inhibits CD8+ T-cell exhaustion and promotes CAR T-cell function
Authors: Kumar Jitendra , Kumar Ritesh , Kumar Singh Amir , Tsakem Elviche L , Kathania Mahesh , Riese Matthew J , Theiss Arianne L , Davila Marco L , Venuprasad K 
Published: January 2021

BackgroundChimeric antigen receptor (CAR) T-cell therapy is an emerging option for cancer treatment, but its efficacy is limited, especially in solid tumors. This is partly because the CAR T cells become dysfunctional and exhausted in the tumor microenvironment. However, the key pathways responsible for impaired function of exhausted cells remain unclear, which is essential to overcome CAR T-cell exhaustion.MethodsAnalysis of RNA-sequencing data from CD8+ tumor-infiltrating lymphocytes (TILs) led to identification of Cbl-b as a potential target. The sequencing data were validated using a syngeneic MC38 colon cancer model. To analyze the in vivo role of Cbl-b in T-cell exhaustion, tumor growth, % PD1+Tim3+ cells, and expression of effector cytokines were analyzed in cbl-b+/+ and cbl-b–/– mice. To evaluate the therapeutic potential of Cbl-b depletion, we generated a new CAR construct, hCEAscFv-CD28-CD3ζ.GFP, that recognizes human carcinoembryonic antigen (CEA). cbl-b+/+ and cbl-b–/– CEA-CAR T cells were generated by retroviral transduction. Rag–/– mice bearing MC38-CEA cells were injected with cbl-b+/+ and cbl-b–/–; CEA-CAR T cells, tumor growth, % PD1+Tim3+ cells and expression of effector cytokines were analyzed.ResultsOur results show that the E3 ubiquitin ligase Cbl-b is upregulated in exhausted (PD1+Tim3+) CD8+ TILs. CRISPR-Cas9-mediated inhibition of Cbl-b restores the effector function of exhausted CD8+ TILs. Importantly, the reduced growth of syngeneic MC38 tumors in cbl-b–/– mice was associated with a marked reduction of PD1+Tim3+ CD8+ TILs. Depletion of Cbl-b inhibited CAR T-cell exhaustion, resulting in reduced MC38-CEA tumor growth, reduced PD1+Tim3+ cells and increased expression of interferon gamma, tumor necrosis factor alpha, and increased tumor cell killing.ConclusionOur studies demonstrate that deficiency of Cbl-b overcomes endogenous CD8+ T-cell exhaustion, and deletion of Cbl-b in CAR T cells renders them resistant to exhaustion. Our results could facilitate the development of efficient CAR T-cell therapy for solid tumors by targeting Cbl-b.
Functional assessment of myocardial ischaemia by intracoronary ECG
Authors: Bigler Marius Reto , Stoller Michael , Praz Fabien , Siontis George C M , Grossenbacher Raphael , Tschannen Christine , Seiler Christian 
Published: January 2021

IntroductionIn patients with chronic coronary syndrome, percutaneous coronary intervention targets haemodynamically significant stenoses, that is, those thought to cause ischaemia. Intracoronary ECG (icECG) detects ischaemia directly where it occurs. Thus, the goal of this study was to test the accuracy of icECG during pharmacological inotropic stress to determine functional coronary lesion severity in comparison to the structural parameter of quantitative angiographic per cent diameter stenosis (%S), as well as to the haemodynamic indices of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR).MethodThe primary study endpoint of this prospective trial was the maximal change in icECG ST-segment shift during pharmacological inotropic stress induced by dobutamine plus atropine obtained within 1 min after reaching maximal heart rate(=220 - age). IcECG was acquired by attaching an alligator clamp to the angioplasty guidewire positioned downstream of the stenosis. For the pressure-derived stenosis severity ratios, coronary perfusion pressure and simultaneous aortic pressure were continuously recorded.ResultsThere was a direct linear relation between icECG ST-segment shift and %S: icECG=−0.8+0.03*%S (r2=0.164; p<0.0001). There were inverse linear correlations between FFR and %S: FFR=1.1–6.1*10–3*%S (r2=0.494; p<0.0001), and between iFR and %S: iFR=1.27–8.6*10–3*%S (r2=0.461; p<0.0001). Using a %S-threshold of ≥50% as the reference for structural stenosis relevance, receiver operating characteristics-analysis of absolute icECG ST-segment shift during hyperemia showed an area under the curve (AUC) of 0.678±0.054 (p=0.002; sensitivity=85%, specificity=50% at 0.34 mV). AUC for FFR was 0.854±0.037 (p<0.0001; sensitivity=64%, specificity=96% at 0.78), and for iFR it was 0.816±0.043 (p<0.0001;sensitivity=62%, specificity=96% at 0.83).ConclusionsHyperaemic icECG ST-segment shift detects structurally relevant coronary stenotic lesions with high sensitivity, while they are identified highly specific by FFR and iFR.
Echocardiographic screening for the anomalous aortic origin of coronary arteries
Authors: Bianco Francesco , Colaneri Massimo , Bucciarelli Valentina , Surace Francesca Chiara , Iezzi Federica Valentina , Primavera Martina , Biasi Annaclara , Giusti Giuliano , Berton Emanuela , Baldoni Monica , Renda Giulia , Baldinelli Alessandra , Gallina Sabina , Pozzi Marco 
Published: January 2021

AimsWe sought to determine the diagnostic performance, clinical profiles and outcomes of anomalous aortic origin of coronary arteries (AAOCA) using a standardised echocardiographic approach in young adults and athletes.MethodsIn 2015–2019, we screened 5998 outpatients (age 16 years (Q1–Q3: 11, 36)), referred for routine echocardiography, using four specific echocardiographic windows: parasternal short/long axis and apical 4/5-chambers view. Coronary CT confirmed AAOCA. For the performance analysis, 300 coronary-CT scans were available; two independent and double-blinded physicians retrospectively reviewed echocardiographic images.ResultsA total of 47 AAOCA was diagnosed; the overall prevalence was 0.0078%. Over 5 years, we found a significant increment of AAOCA diagnostic rate (P for trend=0.002). Syncope (n=17/47) and palpitations (n=6/47) were prevalent symptoms. All patients suspended sports activity at the diagnosis. Twenty-seven patients underwent surgery, while 20 underwent a conservative medical treatment. All patients are alive at a median follow-up of 3±1.6 years; only surgical repairs restarted their activity. Our method showed better sensitivity than traditional short-axis evaluation: 93% vs 83%, p=0.0030 (AUC 0.96 (95% CI 0.92, 0.99) and AUC 0.89 (95% CI 0.83, 0.95), respectively), with a good interobserver agreement (95%, k=0.83, p<0.001).ConclusionsThe application of a standardised echocardiographic approach for AAOCA detection led to a significantly increased rate of identified anomalies. This approach demonstrated higher sensitivity than the traditional echocardiographic assessment. Implementing this protocol in clinical practice may help improve the AAOCA diagnosis in young adults and athletes.Trial registration numberNCT04224090.
Incident hypertension in urban slums of central India: a prospective cohort study
Authors: Pakhare Abhijit P , Lahiri Anuja , Shrivastava Neelesh , Joshi Ankur , Khadanga Sagar , Joshi Rajnish 
Published: January 2021

BackgroundNumerous studies have highlighted the burden of hypertension by estimating its prevalence. However, information regarding quantum and characteristics of persons whose blood pressure converts to hypertension range from their previous state of prehypertension or normal blood pressure is crucial for any public health programme. We aimed to estimate incidence rate of hypertension and to identify risk factors for the same, so that it is useful for programme implementation.MethodsWe established a cohort of adults residing in urban slums of Bhopal, who were registered in a baseline cardiovascular risk assessment survey, which was performed between November 2017 and March 2018. Blood pressure assessment was done at least three times at baseline for diagnosis of hypertension, which was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg on two occasions. Participants who did not have a diagnosis of hypertension were followed up during April–June 2019.ResultsOf the 5673 participants assessed at baseline, 4185 did not have hypertension of which 3199 (76.4%) were followed up after a median on 1.25 years (IQR 1.08–1.60) and a total of 170 (5.31%) individuals were detected with incident hypertension. Overall incidence rate of hypertension was 4.1 (95% CI 3.54 to 4.75) per 100 person-years of follow-up. On multivariate analysis, age (relative risk/RR 1.98; 95% CI 1.19 to 3.3, for age >60 years), being in first and second wealth tertile (T-1 RR 1.85; 95% CI 1.17 to 2.91) and being illiterate (RR 1.94; 95% CI 1.31 to 2.86) were significant predictors of incident hypertension. Individuals who had prehypertension at baseline also had a significantly increased risk of developing hypertension (RR 2.72; 95% CI 1.83 to 4.03).ConclusionsWe found that incidence of hypertension in urban slums of central India is higher with increasing age and in men. Illiteracy, lower Wealth Index and prehypertension are other determinants. We also demonstrate feasibility of establishing a cohort within the public health delivery system, driven by efforts of community health workers.