bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholinergic and inflammatory phenotypes in transgenic tau mouse models of Alzheimer’s disease and frontotemporal lobar degeneration
Authors: Cranston Anna L , Wysocka Adrianna , Steczkowska Marta , Zadrożny Maciej , Palasz Ewelina , Harrington Charles R , Theuring Franz , Wischik Claude M , Riedel Gernot , Niewiadomska Grazyna 
Published: March 2020

AbstractAn early and sizeable loss of basal forebrain cholinergic neurons is a well-characterized feature associated with measurable deficits in spatial learning and cognitive impairment in patients with Alzheimer’s disease. In addition, pro-inflammatory glial cells such as astrocytes and microglia may play a key role in the neurodegenerative cascade of Alzheimer’s disease and tauopathies. We recently presented two mouse models: Line 1, expressing the truncated tau fragment identified as the core of the Alzheimer’s paired helical filament, and Line 66, expressing full-length human tau carrying a double mutation (P301S and G335D). Line 1 mice have a pathology that is akin to Alzheimer’s, whilst Line 66 resembles frontotemporal lobar degeneration. However, their cholinergic and inflammatory phenotypes remain elusive. We performed histological evaluation of choline acetyltransferase, acetylcholinesterase, p75 neurotrophin receptor, microglial ionized calcium binding adaptor molecule 1 and astrocytic glial fibrillary acidic protein in the basal forebrain, hippocampus and cortex of these models. A significant lowering of choline acetyltransferase-positive neurons and p75-positive neurons in the basal forebrain of Line 1 at 3, 6 and 9 months was observed in two independent studies, alongside a significant decrease in acetylcholinesterase staining in the cortex and hippocampus. The reductions in choline acetyltransferase positivity varied between 30% and 50% at an age when Line 1 mice show spatial learning impairments. Furthermore, an increase in microglial ionized calcium binding adaptor molecule 1 staining was observed in the basal forebrain, hippocampus and entorhinal cortex of Line 1 at 6 months. Line 66 mice displayed an intact cholinergic basal forebrain, and no difference in p75-positive neurons at 3 or 9 months. In addition, Line 66 exhibited significant microglial ionized calcium binding adaptor molecule 1 increase in the basal forebrain and hippocampus, suggesting a prominent neuroinflammatory profile. Increased concentrations of microglial interleukin-1β and astrocytic complement 3 were also seen in the hippocampus of both Line 1 and Line 66. The cholinergic deficit in Line 1 mice confirms the Alzheimer’s disease-like phenotype in Line 1 mice, whilst Line 66 revealed no measurable change in total cholinergic expression, a phenotypic trait of frontotemporal lobar degeneration. These two transgenic lines are therefore suitable for discriminating mechanistic underpinnings between the Alzheimer’s and frontotemporal lobar degeneration-like phenotypes of these mice.
The Subplate Layers: The Superficial and Deep Subplate Can be Discriminated on 3 Tesla Human Fetal Postmortem MRI
Authors: Pogledic Ivana , Schwartz Ernst , Mitter Christian , Baltzer Pascal , Milos Ruxandra-Iulia , Gruber Gerlinde Maria , Brugger Peter C , Hainfellner Johannes , Bettelheim Dieter , Langs Georg , Kasprian Gregor , Prayer Daniela 
Published: March 2020

Abstract
The subplate (SP) is a transient structure of the human fetal brain that becomes the most prominent layer of the developing pallium during the late second trimester. It is important in the formation of thalamocortical and cortico-cortical connections. The SP is vulnerable in perinatal brain injury and may play a role in complex neurodevelopmental disorders, such as schizophrenia and autism. Nine postmortem fetal human brains (19–24 GW) were imaged on a 3 Tesla MR scanner and the T2-w images in the frontal and temporal lobes were compared, in each case, with the histological slices of the same brain. The brains were confirmed to be without any brain pathology. The purpose of this study was to demonstrate that the superficial SP (sSP) and deep SP (dSP) can be discriminated on postmortem MR images. More specifically, we aimed to clarify that the observable, thin, hyperintense layer below the cortical plate in the upper SP portion on T2-weighted MR images has an anatomical correspondence to the histologically established sSP. Therefore, the distinction between the sSP and dSP layers, using clinically available MR imaging methodology, is possible in postmortem MRI and can help in the imaging interpretation of the fetal cerebral layers.
Clinical Features and Short-term Outcomes of 102 Patients with Coronavirus Disease 2019 in Wuhan, China
Authors: Cao Jianlei , Tu Wen-Jun , Cheng Wenlin , Yu Lei , Liu Ya-Kun , Hu Xiaorong , Liu Qiang 
Published: March 2020

AbstractBackgroundIn December 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, Hubei, China. In this study, we investigate the clinical and laboratory features and short-term outcomes of patients with coronavirus disease 2019 (COVID-19).MethodsAll patients with COVID-19 admitted to Wuhan University Zhongnan Hospital in Wuhan, China, between 3 January and 1 February 2020 were included. All those patients were with laboratory-confirmed infections. Epidemiological, clinical, and radiological characteristics; underlying diseases; laboratory tests; treatments; complications; and outcomes data were collected. Outcomes were followed up at discharge until 15 February 2020.ResultsThe study cohort included 102 adult patients. The median age was 54 years (interquartile ranger, 37–67 years), and 48.0% were female. A total of 34 patients (33.3%) were exposed to a source of transmission in the hospital setting (as health-care workers, patients, or visitors) and 10 patients (9.8%) had a familial cluster. There were 18 patients (17.6%) who were admitted to the intensive care unit (ICU), and 17 patients died (mortality, 16.7%; 95% confidence interval, 9.4–23.9%). Those patients who survived were younger, were more likely to be health-care workers, and were less likely to suffer from comorbidities. They were also less likely to suffer from complications. There was no difference in drug treatment rates between the survival and nonsurvival groups. Those patients who survived were less likely to require admission to the ICU (14.1% vs 35.3% of those admitted). Chest imaging examinations showed that patients who died were more likely to have ground-glass opacity (41.2% vs 12.9% in survivors).ConclusionsThe mortality rate was high among the COVID-19 patients described in our cohort who met our criteria for inclusion in this analysis. The patient characteristics seen more frequently in those who died were the development of systemic complications following onset of the illness and a severity of disease requiring admission to the ICU. Our data support those described by others indicating that COVID-19 infection results from human-to-human transmission, including familial clustering of cases, and from nosocomial transmission. There were no differences in mortality among those who did or did not receive antimicrobial or glucocorticoid drug treatments.
Prevalence and Sequelae of Cryptococcal Antigenemia in Antiretroviral Therapy–Experienced Populations: An Evaluation of Reflex Cryptococcal Antigen Screening in Botswana
Authors: Hurt William J , Tenforde Mark W , Molefi Mooketsi , Mitchell Hannah K , Milton Thandi , Azama Martin S , Goercke Irene , Mulenga Fredah , Tlhako Nametso , Tsholo Katlego , Srivastava Tuhina , Leeme Tshepo B , Simoonga Godfrey , Muthoga Charles , Lechiile Kwana , Mine Madisa , Jarvis Joseph N 
Published: March 2020

Abstract

Background
Evidence to inform cryptococcal antigen (CrAg)–screening guidelines among ART-experienced populations is lacking. We performed a study evaluating the utility of reflex CrAg screening in Gaborone, Botswana.

Methods
CD4 count data were collected from the HIV reference laboratory from 2014–2016. CrAg screening was performed on samples with CD4 ≤100 cells/µL beginning January 2015. The proportion of CD4 counts ≤100 cells/µL was determined and the frequency of repeat CrAg testing described. Analyses ascertained the impact of ART status on CrAg prevalence and outcomes, and whether CrAg titers could be used for risk stratification.

Results
Overall, 5.6% (3335/59 300) of individuals tested had CD4 ≤100 cells/μL; 2108 samples with CD4 ≤100 cells/μL from 1645 unique patients were CrAg tested. Over half of samples were from ART-experienced individuals: 40.9% (863) on ART and 12.1% (255) defaulters; 22% (463) of CrAg tests were on repeat samples. CrAg prevalence was 4.8% (72/1494; 95% CI, 3.8–6.0%) among outpatients and 21.9% (32/151; 95% CI, 15.3–28.5%) among inpatients. CrAg prevalence rates did not differ by ART status, but 6-month mortality was significantly lower in CrAg-positive individuals on ART at screening. Ten CrAg positives were identified through repeat testing. A CrAg titer cutoff ≥1:80 provided the best discrimination for 6-month survival.

Conclusions
CrAg-positivity rates in an ART-experienced population were comparable to those seen in ART-naive populations. Repeat screening identified individuals who seroconverted to CrAg positivity and were at risk of cryptococcal disease. CrAg titers ≥1:80 can help identify the individuals at highest risk of death for more intensive management.
Isavuconazole as Primary Antifungal Prophylaxis in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome: An Open-label, Prospective, Phase 2 Study
Authors: Bose Prithviraj , McCue David , Wurster Sebastian , Wiederhold Nathan P , Konopleva Marina , Kadia Tapan M , Borthakur Gautam , Ravandi Farhad , Masarova Lucia , Takahashi Koichi , Estrov Zeev , Yilmaz Musa , Daver Naval , Pemmaraju Naveen , Naqvi Kiran , Rausch Caitlin R , Marx Kayleigh R , Qiao Wei , Huang Xuelin , Bivins Carol A , Pierce Sherry A , Kantarjian Hagop M , Kontoyiannis Dimitrios P 
Published: March 2020

Abstract

Background
Mold-active primary antifungal prophylaxis (PAP) is routinely recommended in neutropenic patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing remission-induction chemotherapy (RIC). Isavuconazole (ISAV) is an extended spectrum mold-active triazole and has superior tolerability and fewer significant drug–drug interactions compared with other triazoles.

Methods
In our investigator-initiated, phase 2 trial, treatment-naive adult patients with AML or MDS starting RIC received ISAV per the dosing recommendations in the US label until neutrophil recovery (absolute neutrophil count [ANC] ≥ 0.5 × 109/L) and attainment of complete remission, occurrence of invasive fungal infection (IFI), or for a maximum of 12 weeks. The primary endpoint was the incidence of proven/probable IFI during ISAV PAP and up to 30 days after the last dose.

Results
Sixty-five of 75 enrolled patients received ISAV PAP (median age, 67 years, median ANC at enrollment, 0.72 × 109/L). Thirty-two patients (49%) received oral targeted leukemia treatments (venetoclax, FTL3 inhibitors). Including the 30-day follow-up period, probable/proven and possible IFIs were encountered in 4 (6%) and 8 patients (12%), respectively. ISAV trough serum concentrations were consistently &gt; 1 µg/mL, showed low intraindividual variation, and were not significantly influenced by chemotherapy regimen. Tolerability of ISAV was excellent, with only 3 cases (5%) of mild to moderate elevations of liver function tests and no QTc prolongations.

Conclusions
ISAV is a safe and effective alternative for PAP in patients with newly diagnosed AML/MDS undergoing RIC in the era of recently approved or emerging small-molecule antileukemia therapies.

Clinical Trials Registration
NCT03019939.
Character Recognition Algorithm Based on Fusion Probability Model and Deep Learning
Authors: Liu Zhijun , Pan Xuefeng , Peng Yuan 
Published: March 2020

Abstract
The authors proposed a character recognition algorithm to improve the recognition efficiency and recognition accuracy in character recognition. The algorithm is based on a deep belief network classifier. In the character recognition, a comprehensive feature model is established firstly by combining the histogram Gabor feature, grid level feature and gray level co-occurrence matrix. Subsequently, the deep belief network trains the feature model. Finally, the probability model is used to judge the recognition symbols. The algorithm is tested with 74 k data set and is compared and analyzed from three indexes: false acceptance rate, false rejection rate and accuracy. The data set simulation and comparison with other algorithms indicate that the recognition system based on the probability model and depth learning has higher accuracy and better performance.
Collective memory and Spanish cultural politics: the revival of the Roman theatre of Merida (1910–35)
Authors: Balaskas Vasileios 
Published: March 2020

Abstract
In the twentieth century, ancient theatres acquired symbolic values through their excavation, restoration, and cultural reuse. While elsewhere in the Mediterranean comparable cases show an early and powerful engagement of a populace with their antiquities, in Spain national ideals did not automatically engage with classical culture. In the case of the Roman theatre of Merida, cultural and historical realities dictated a series of cultural events that repeatedly concerned collective memory. In addition to the main sequence of the unique occasions surrounding the 1933 and 1934 performances at the theatre, various other agencies had systematically focused on its exploitation from the 1910s. These initiatives were endorsed by numerous formal visits and cultural events that took place in the theatre, from as early as 1914. Through successive spectacles staged at the theatre, a cultural tradition emerged, while political agendas occasionally exploited its increasing popularity, right up to the Spanish Civil War.
Circulating uromodulin inhibits vascular calcification by interfering with pro-inflammatory cytokine signalling
Authors: Alesutan Ioana , Luong Trang T D , Schelski Nadeshda , Masyout Jaber , Hille Susanne , Schneider Markus P , Graham Delyth , Zickler Daniel , Verheyen Nicolas , Estepa Misael , Pasch Andreas , Maerz Winfried , Tomaschitz Andreas , Pilz Stefan , Frey Norbert , Lang Florian , Delles Christian , Müller Oliver J , Pieske Burkert , Eckardt Kai-Uwe , Scherberich Juergen , Voelkl Jakob 
Published: March 2020

Abstract

Aims
Uromodulin is produced exclusively in the kidney and secreted into both urine and blood. Serum levels of uromodulin are correlated with kidney function and reduced in chronic kidney disease (CKD) patients, but physiological functions of serum uromodulin are still elusive. This study investigated the role of uromodulin in medial vascular calcification, a key factor associated with cardiovascular events and mortality in CKD patients.

Methods and results
Experiments were performed in primary human (HAoSMCs) and mouse (MOVAS) aortic smooth muscle cells, cholecalciferol overload and subtotal nephrectomy mouse models and serum from CKD patients. In three independent cohorts of CKD patients, serum uromodulin concentrations were inversely correlated with serum calcification propensity. Uromodulin supplementation reduced phosphate-induced osteo-/chondrogenic transdifferentiation and calcification of HAoSMCs. In human serum, pro-inflammatory cytokines tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) co-immunoprecipitated with uromodulin. Uromodulin inhibited TNFα and IL-1β-induced osteo-/chondrogenic signalling and activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated β cells (NF-kB) as well as phosphate-induced NF-kB-dependent transcriptional activity in HAoSMCs. In vivo, adeno-associated virus (AAV)-mediated overexpression of uromodulin ameliorated vascular calcification in mice with cholecalciferol overload. Conversely, cholecalciferol overload-induced vascular calcification was aggravated in uromodulin-deficient mice. In contrast, uromodulin overexpression failed to reduce vascular calcification during renal failure in mice. Carbamylated uromodulin was detected in serum of CKD patients and uromodulin carbamylation inhibited its anti-calcific properties in vitro.

Conclusions
Uromodulin counteracts vascular osteo-/chondrogenic transdifferentiation and calcification, at least in part, through interference with cytokine-dependent pro-calcific signalling. In CKD, reduction and carbamylation of uromodulin may contribute to vascular pathology.
Successful implantation of leadless pacemakers in children: a case series
Authors: Jędrzejczyk-Patej Ewa , Woźniak Aleksandra , Litwin Linda , Skiba-Zdrzałek Alina , Mazurek Michał , Lenarczyk Radosław , Kalarus Zbigniew , Kowalski Oskar 
Published: March 2020

Abstract

Background
A leadless pacemaker is a new concept in which a miniaturized pacing device is self-contained within the heart. Recently published data show that leadless pacemakers are associated with a decreased risk of major complications when compared with transvenous cardiac pacemakers. This seems to be of particular importance in children and young adults in whom various complications may occur during their lifetime.

Case summary
Herein, we report the successful implantation of Micra™ Transcatheter Pacing System in two children: 12-year-old boy and 13-year-old girl, along with a long-term follow-up. The children had indications for pacemaker implantation, however, with an expected low percentage of pacing due to paroxysmal nature of the third-degree atrioventricular block. The implantation procedures were performed in general anaesthesia. There were no complications. During the 2-year follow-up, there were no adverse events and the electrical parameters of the device remained stable. Pacing percentage was below 0.1%.

Discussion
Transvenous cardiac pacemakers improve quality of life and reduce mortality but may be associated with various short- and long-term complications, mainly related to the presence of transvenous leads and the pulse generator. Compared with adult patients, the implantation of conventional pacemakers in children is still a challenge, not only because of their smaller size but also due to continuing growth, as well as a higher rate of lead and device-related complications. We demonstrate that the implantation of leadless pacemakers in children is feasible and could be worth considering in certain clinical scenarios, especially when ventricular pacing is required rarely.
Battista Carioni da Crema (c.1460–1534) and the ‘Third Life’: Visions of Reform in Early Sixteenth-Century Italy
Authors: Mazzonis Querciolo 
Published: March 2020

Abstract
This essay sheds new light on the spirituality and historical significance of the influential and controversial Dominican friar Battista Carioni da Crema (c.1460–1534). A popular spiritual writer, charismatic founder of devout associations such as the Barnabites, and a spiritual director of several well-known Catholic figures, including Gaetano Thiene, Battista’s significance has not yet been fully acknowledged. The essay considers his spirituality in the framework of reforming movements emerging in Italy in the first half of the sixteenth century. In dialogue with previous interpretations of Battista, the essay provides a novel and systematic analysis of his notion of perfection and concept of the Church. Synthesising ascetic and mystic spiritual influences rooted in the monastic and humanist culture of the fifteenth century, Battista presented a distinctive view of Christian life, which included an ecclesiological perspective and a new geography of the sacred. Defined as the ‘third life’ and conceived in a period of religious fluidity, it neither fitted emerging Lutheran ideas nor the orthodox Catholicism of the Roman Church. In addition, the essay argues that Battista’s proselytism can be seen as an attempt to reform society which preceded proposals for religious reform made by groups such as the Spirituali.
Adherence to and Retention in Medications for Opioid Use Disorder Among Adolescents and Young Adults
Authors: Viera Adam , Bromberg Daniel J , Whittaker Shannon , Refsland Bryan M , Stanojlović Milena , Nyhan Kate , Altice Frederick L 
Published: March 2020

Abstract
The volatile opioid epidemic is associated with higher levels of opioid use disorder (OUD) and negative health outcomes in adolescents and young adults. Medications for opioid use disorder (MOUD) demonstrate the best evidence for treating OUD. Adherence to and retention in MOUD, defined as continuous engagement in treatment, among adolescents and young adults, however, is incompletely understood. We examined the state of the literature regarding the association of age with adherence to and retention in MOUD using methadone, buprenorphine, or naltrexone among persons aged 10–24 years, along with related facilitators and barriers. All studies of MOUD were searched for that examined adherence, retention, or related concepts as an outcome variable and included adolescents or young adults. Search criteria generated 10,229 records; after removing duplicates and screening titles and abstracts, 587 studies were identified for full-text review. Ultimately, 52 articles met inclusion criteria for abstraction and 17 were selected for qualitative coding and analysis. Younger age was consistently associated with shorter retention, although the overall quality of included studies was low. Several factors at the individual, interpersonal, and institutional levels, such as concurrent substance use, MOUD adherence, family conflict, and MOUD dosage and flexibility, appeared to have roles in MOUD retention among adolescents and young adults. Ways MOUD providers can tailor treatment to increase retention of adolescents and young adults are highlighted, as is the need for more research explaining MOUD adherence and retention disparities in this age group.
When genetic burden reaches threshold
Authors: Walsh Roddy , Tadros Rafik , Bezzina Connie R 
Published: March 2020

Abstract
Rare cardiac genetic diseases have generally been considered to be broadly Mendelian in nature, with clinical genetic testing for these conditions predicated on the detection of a primary causative rare pathogenic variant that will enable cascade genetic screening in families. However, substantial variability in penetrance and disease severity among carriers of pathogenic variants, as well as the inability to detect rare Mendelian variants in considerable proportions of patients, indicates that more complex aetiologies are likely to underlie these diseases. Recent findings have suggested genetic variants across a range of population frequencies and effect sizes may combine, along with non-genetic factors, to determine whether the threshold for expression of disease is reached and the severity of the phenotype. The availability of increasingly large genetically characterized cohorts of patients with rare cardiac diseases is enabling the discovery of common genetic variation that may underlie both variable penetrance in Mendelian diseases and the genetic aetiology of apparently non-Mendelian rare cardiac conditions. It is likely that the genetic architecture of rare cardiac diseases will vary considerably between different conditions as well as between patients with similar phenotypes, ranging from near-Mendelian disease to models more akin to common, complex disease. Uncovering the broad range of genetic factors that predispose patients to rare cardiac diseases offers the promise of improved risk prediction and more focused clinical management in patients and their families.