bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical landscape of oncolytic virus research in 2020
Authors: Macedo Nicholas , Miller David M , Haq Rizwan , Kaufman Howard L
Published: October 2020

Oncolytic viruses (OVs) are a new class of cancer therapeutics. This review was undertaken to provide insight into the current landscape of OV clinical trials. A PubMed search identified 119 papers from 2000 to 2020 with 97 studies reporting data on 3233 patients. The viruses used, presence of genetic modifications and/or transgene expression, cancer types targeted, inclusion of combination strategies and safety profile were reported. In addition, information on viral bioshedding across the studies, including which tissues or body fluids were evaluated and how virus was detected (eg, PCR, plaque assay or both), is also reported. Finally, the number of studies evaluating antiviral and antitumor humoral and cellular immune responses were noted. We found that adenovirus (n=30) is the most common OV in clinical trials with approximately two-thirds (n=63) using modified or recombinant viral backbones and granulocyte-macrophage colony-stimulating factor (n=24) was the most common transgene. The most common tumors targeted were melanoma (n=1000) and gastrointestinal (GI; n=577) cancers with most using monotherapy OVs given by intratumoral (n=1482) or intravenous (n=1347) delivery. The most common combination included chemotherapy (n=36). Overall, OV treatment-related adverse events were low-grade constitutional and local injection site reactions. Viral shedding was frequently measured although many studies restricted this to blood and tumor tissue and used PCR only. While most studies did report antiviral antibody titers (n=63), only a minority of studies reported viral-specific T cell responses (n=10). Tumor immunity was reported in 48 studies and largely relied on general measures of immune activation (eg, tumor biopsy immunohistochemistry (n=25) and serum cytokine measurement (n=19)) with few evaluating tumor-specific immune responses (n=7). Objective responses were reported in 292 (9%) patients and disease control was achieved in 681 (21.1%) patients, although standard reporting criteria were only used in 53% of the trials. Completed clinical trials not reported in the peer-reviewed literature were not included in this review potentially underestimating the impact of OV treatment. These data provide insight into the current profile of OV clinical trials reporting and identifies potential gaps where further studies are needed to better define the role of OVs, alone and in combination, for patients with cancer.
Anti-Aβ agents for mild to moderate Alzheimer's disease: systematic review and meta-analysis
Authors: Lu Liming , Zheng Xiaoyan , Wang Shengwen , Tang Chunzhi , Zhang Yuqing , Yao Gaolei , Zeng Jingchun , Ge Shuqi , Wen Hao , Xu Mingzhu , Guyatt Gordon , Xu Nenggui
Published: October 2020

Objective

To assess the efficacy and safety of Aβ-targeting agents for mild to moderate Alzheimer’s disease.

Methods

The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses.

Results

Nineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer’s Disease Assessment Scale (ADAS-Cog) between anti-Aβ drugs and placebo (mean difference (MD): 0.20, 95% CI −0.40 to 0.81;
I
2
=99.8%; minimal important difference 3.1–3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aβ clearance may differ in effect (MD: −0.96, 95% CI −0.99 to −0.92) from drugs that reduce Aβ production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aβ drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit.

Discussion

From current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small.

Trial registration number

PROSPERO registration number CRD42019126272.
Improving Voting Feature Intervals for Spatial Prediction of Landslides
Authors: Pham Binh Thai , Phong Tran Van , Avand Mohammadtaghi , Al-Ansari Nadhir , Singh Sushant K. , Le Hiep Van , Prakash Indra
Published: October 2020

In this study, the main aim is to improve performance of the voting feature intervals (VFIs), which is one of the most effective machine learning models, using two robust ensemble techniques, namely, AdaBoost and MultiBoost for landslide susceptibility assessment and prediction. For this, two hybrid models, namely, AdaBoost-based Voting Feature Intervals (ABVFIs) and MultiBoost-based Voting Feature Intervals (MBVFIs) were developed and validated using landslide data collected from one of the landslide affected districts of Vietnam, namely, Muong Lay. Quantitative validation methods including area under the ROC curve (AUC) were used to evaluate model performance. The results indicated that both the newly developed ensemble models ABVFI (AUC = 0.859) and MBVFI (AUC = 0.839) outperformed the single VFI (AUC = 0.824) model. Thus, ensemble framework-based VFI algorithms can be used for the accurate spatial prediction of landslides, which can also be applied in other landslide prone regions of the world. Landslide susceptibility maps developed by ensemble VFI models can be used for better landslide prevention and risk management of the area.
El papel emergente de la radiómica en la EPOC y el cáncer de pulmón
Authors: Refaee Turkey , Wu Guangyao , Ibrahim Abdallah , Halilaj Iva , Leijenaar Ralph T.H. , Rogers William , Gietema Hester A. , Hendriks Lizza E.L. , Lambin Philippe , Woodruff Henry C.
Published: October 2020

La imagenología médica tiene un papel clave en la evaluación y el monitoreo de enfermedades pulmonares como la enfermedad pulmonar obstructiva crónica (EPOC) y el cáncer de pulmón. La aplicación de la inteligencia artificial ha transformado las imágenes médicas en datos susceptibles de minería, al extraer y correlacionar características imagenológicas cuantitativas con los resultados del paciente y el fenotipo de un tumor, en un proceso denominado radiómica. Aunque hay extensas investigaciones sobre la aplicación del proceso en oncología pulmonar, la evaluación de la EPOC mediante radiómica aún está en su infancia. En este trabajo describimos las principales aplicaciones de la radiómica en el cáncer de pulmón y revisamos brevemente el flujo de trabajo, desde la adquisición de imágenes hasta la evaluación del desempeño del modelo. Finalmente, discutimos los medios actuales para valorar la EPOC y la aplicación potencial de la radiómica en esta enfermedad.
Impact of Extended Treatment Interval on the Prognosis of Multiple Myeloma Patients: A Retrospective Study
Authors: Sun Chao , Ye Jian-Nan , Mao Jing-Jue , Ma Ke-Wa , Zhou Xin
Published: October 2020

Introduction: Recently, treatment with proteasome inhibitors and immunomodulators has improved the prognosis of multiple myeloma (MM). However, in a complex real-world situation, the patient’s ability to undergo regular and timely treatment as prescribed in clinical trials has not been studied, as well as the impact of extended treatment intervals due to different reasons. This study aimed to evaluate the treatment interval and clinical characteristics of 122 patients with primary myeloma in our hospital and explore the prognostic effects of different treatment intervals. Methods: In total, 122 patients with MM were analyzed retrospectively in our hospital from January 2007 to June 2018. The clinical and laboratory data (such as age, International Staging System [ISS] stage, chromosome, etc.) and subsequent treatment intervals were analyzed. The Cox proportional hazard regression model was used for univariate and multivariate analyses of overall survival (OS) and progression-free survival. The Kaplan-Meier method was used in survival analysis, and the log-rank test was used to test survival difference. p < 0.05 was considered to indicate statistical significance. Results: We found that prolonging the interval treatments (>28 days) shortened the OS in the younger and high-risk subgroups. On the contrary, the OS of the older and low-risk subgroups was not shortened. OS was also shortened in patients who were suitable for transplantation but did not receive a transplant. Univariate and multivariate analyses showed that extension of treatment interval was a risk factor for OS shortening. In addition, prolonged treatment interval was due to iatrogenic and family reasons. Conclusion: Extended treatment interval is unfavorable in young and high-risk MM patients and those suitable for transplantation but who did not receive a transplant. However, it has a faint impact on the elderly and low-risk subgroups.
Adenocarcinoma de pulmón que simula tuberculosis miliar
Authors: Khan Dawlat , Danjuma Mohammed , Saddique Muhammad Umar , Murshed Khaled A. , Yassin Mohamed A.
Published: October 2020

Las sombras miliares en imágenes del tórax tienen diagnósticos diferenciales muy diversos. La etiología más común es infecciosa, como la tuberculosis (TB) miliar y la histoplasmosis, pero las sombras miliares pueden ser la presentación de la sarcoidosis, neumoconiosis y metástasis secundaria al pulmón de cánceres primarios de tiroides, riñón y trofoblastos, así como del sarcoma. Presentamos el caso de un paciente indio, masculino, quien refirió una historia de dos meses con tos seca y dificultad respiratoria. Imágenes del tórax mostraron nódulos miliares bilaterales, difusos. La impresión inicial fue TB pulmonar miliar. Una posterior broncoscopía con biopsia transbronquial confirmó el diagnóstico de adenocarcinoma mucinoso pulmonar con metástasis al cerebro, una presentación rara e inusual de cáncer de pulmón primario. El tumor fue positivo para ALK5A4 y PD-L1, y se inició inmunoterapia con un inhibidor de tirosina quinasa, con respuesta favorable.
CPCNP en estadio II: radioterapia y uso de quimioterapia en pacientes inoperables
Authors: Möller Miriam , Schütte Wolfgang
Published: October 2020

Objectives: Curative intent therapy of stage II NSCLC may include surgical resection or definitive radiotherapy. Primary management with surgery or radiotherapy may be influenced by patient and disease characteristics. We sought to perform a comparison of patients receiving surgery or radical radiation therapy as their curative treatment, and explore the impact of known prognostic factors on outcome. Materials and methods: A retrospective review was completed of all patients with stage II NSCLC referred to the BC Cancer Agency from 2005 to 2012. Cases were filtered to identify those receiving curative intent therapy including surgery or radiotherapy. Information was collected on known prognostic and predictive factors. The primary outcome measure was overall survival. We compared survival among patients receiving curative intent radiotherapy versus surgical intervention. Results: A total of 535 patients were referred. Of these, 245 (46%) received curative intent surgery, 132 (25%) curative intent radiotherapy, and 158 (30%) did not receive curative therapy. There were significant differences between cohorts with respect to median age, histology, ECOG PS, smoking status, and weight loss. Median OS was significantly different between cohorts: 61.4 m surgery, 26.5 m curative RT, and 13.1 m non-curative therapy. In a case-matched analysis, median OS remained superior for surgery at 101.6 m vs 28.1 m for curative RT. In a multivariate analysis, ECOG PS, weight loss, and treatment cohort all influenced survival. Among patients receiving curative intent radiotherapy, the use of concurrent chemotherapy and RT dose ≥ 60 Gy were associated with improved outcomes. Conclusions: Among patients with stage II NSCLC, many are unable to undergo standard of care surgical resection. Radiotherapy provides an inferior yet still curative option in the management of inoperable patients. Further work is needed to optimize outcomes in this population.
Calcitonin Levels in Thyroid Disease Are Not Affected by Autoimmune Thyroiditis or Differentiated Thyroid Carcinoma
Authors: Maino Fabio , Dalmiglio Cristina , Benenati Nicoletta , Campanile Michele , Pilli Tania , Forleo Raffaella , Brilli Lucia , Ciuoli Cristina , Cantara Silvia , Capezzone Marco , Cartocci Alessandra , Pacini Furio , Castagna Maria Grazia
Published: October 2020

Introduction: Association between hypercalcitoninemia and pathological conditions such as autoimmune thyroiditis (AIT) or differentiated thyroid carcinoma (DTC) has been addressed, with conflicting results. We evaluated the prevalence and the clinical relevance of elevated basal serum calcitonin (CT) levels in non-neoplastic (nodular goiter [NG] and AIT) and neoplastic thyroid diseases (DTC). Methods: We retrospectively evaluated 3,250 consecutive patients with thyroid nodular disease who underwent fine-needle aspiration cytology with adequate sample. After exclusion of medullary thyroid cancer (MTC) patients were divided according to the presence/absence of thyroid autoimmunity into NG or nodular autoimmune thyroiditis (N-AIT) and, according to cytological results, in benign or suspicious/malignant nodules. Results: One hundred ninety-seven/3,250 patients (6.0%) showed CT level >10 pg/mL. In 11/3,250 (0.3%) cases, a final histological diagnosis of MTC was made, while the remaining 186/3,250 patients (5.7%) had non-MTC-related hypercalcitoninemia (CT > 10 pg/mL). According to cytological diagnosis, the rate of hypercalcitoninemia was similar in class II and class V–VI groups (5.4 vs. 6.9%, p = 0.4). The occurrence of hypercalcitoninemia was significantly higher in patients with NG (166/2,634 [6.3%]) than in patients with N-AIT (20/605 [3.3%]) (p = 0.004). However, after matching by sex, no difference was found between the 2 groups (NG and N-AIT). These results were confirmed in 598 patients submitted to surgery. Conclusions: AIT and DTC seem not to affect serum CT levels in patients with thyroid nodules. Therefore, hypercalcitoninemia, in these patients, should be submitted to the same diagnostic workup than patients without AIT or DTC.
Characteristics of Myelogram in Patients with Extraocular Metastatic Retinoblastoma and Morphological Analysis of Tumor Cells in Bone Marrow and Cerebrospinal Fluid
Authors: Song Lijie , Wang Yufei , Zhang Wei , Zhang Dandan , Wang Xiumei , Wang Zhenghui , Zhao Yiwen , Zhang Cui , Duan Cuijuan , Sun Tao , Zhang Liping , Yang Xiaoli
Published: October 2020

Background: Retinoblastoma (RB) is a common intraocular malignant tumor in infants and young children. However, reports on the morphological descriptions of RB tumor cells from native and foreign scholars are rare. Objectives: To investigate the myelogram characteristics of RB with extraocular tumor extension and the morphological characteristics of tumor cells in the bone marrow and cerebrospinal fluid. Methods: For the period from May 2011 to February 2015, we analyzed clinical data on 18 patients in our hospital diagnosed as having metastatic RB in the extraocular and other distant regions associated with clear bone marrow metastasis. The morphology of tumor cells in the bone marrow and cerebrospinal fluid was retrospectively analyzed after staining with Wright-Giemsa stain. A summary of the cytological characteristics was also presented. Results: RB tumor cells in the bone marrow and cerebrospinal fluid not only appeared as aggregated clumps, but were distributed in a scattered manner. The tumor cells may present different characteristic morphologies in different cases, with different tumor cell smears from the same tumor mass even showing different features. According to the degree of tumor metastasis, changes in myelogram were significantly different. Conclusion: The tumor cells of RB patients show unique morphological characteristics in the bone marrow and cerebrospinal fluid. Therefore, correct identification of the cells is of great value in the diagnosis, staging, and prognosis of RB.
Prognostic Value of Quantitative Flow Ratio Based Functional SYNTAX Score in Patients With Left Main or Multivessel Coronary Artery Disease
Authors: Zhang Rui , Song Chenxi , Guan Changdong , Liu Qianqian , Wang Chunyue , Xie Lihua , Sun Zhongwei , Cai Minsi , Zhang Min , Wang Huan , Liu Jian , Dou Kefei , Xu Bo
Published: October 2020

Background:

The potential impact of quantitative flow ratio (QFR) based functional Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (FSS
QFR
) on prognostication and revascularization strategy choice has not been fully investigated, and the discriminant ability of FSS
QFR
needs further validation.

Methods:

QFR was retrospectively analyzed in left main or patients with multivessel coronary artery disease from the PANDA III trial. A total of 607 patients with analyzable QFR in all vessels were included. FSS
QFR
was counted by summing the individual scores only in ischemia-producing lesions (vessel QFR ≤0.8). Patients were stratified according to tertiles of SYNTAX score (SS), and 3 groups of FSS were divided by the same cutoff score. The primary end point was 2-year major adverse cardiac events (a composite of cardiac death, any myocardial infarction, or ischemia-driven revascularization).

Results:

After calculating the FSS
QFR
, 16% (96/607) of study patients moved from higher-risk group by SS to lower-risk group. In the low, intermediate, and high FSS
QFR
group, the cumulative incidence of 2-year major adverse cardiac events was 9.1%, 13.5%, and 22.3% (
P
=0.0004), and the rate of a composite of cardiac death or myocardial infarction (3.8%, 7.3%, and 13.7%,
P
=0.0006) was also increased. Compared with SS, FSS
QFR
significantly improved risk classification and prognostication (area under the curve of the receiver-operating characteristics 0.65 versus 0.62,
P
=0.0009). Moreover, 6% (38/607) of patients, for whom coronary artery bypass grafting would be recommended according to SS, converted to favor percutaneous coronary intervention after FSS
QFR
calculation. After multivariate adjustment, FSS
QFR
was an independent predictor of 2-year major adverse cardiac events (adjusted hazard ratio, 1.05 [95% CI, 1.02–1.07];
P
=0.0001).

Conclusions:

Among patients with left main or multivessel coronary artery disease, FSS
QFR
showed applicability in prognostication and revascularization strategy choice. An improved scoring system combining anatomy and physiology (FSS
QFR
) discriminated the risk of adverse events modestly better than anatomic assessment (SS) alone.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02017275.

Graphic Abstract:

A
graphic abstract
is available for this article.
ATAC-Seq Reveals an
Isl1
Enhancer That Regulates Sinoatrial Node Development and Function
Authors: Galang Giselle , Mandla Ravi , Ruan Hongmei , Jung Catherine , Sinha Tanvi , Stone Nicole R. , Wu Roland S. , Mannion Brandon J. , Allu Prasanna K.R. , Chang Kevin , Rammohan Ashwin , Shi Marie B. , Pennacchio Len A. , Black Brian L. , Vedantham Vasanth
Published: October 2020

Rationale:

Cardiac pacemaker cells (PCs) in the sinoatrial node (SAN) have a distinct gene expression program that allows them to fire automatically and initiate the heartbeat. Although critical SAN transcription factors, including Isl1 (Islet-1), Tbx3 (T-box transcription factor 3), and Shox2 (short-stature homeobox protein 2), have been identified, the
cis
-regulatory architecture that governs PC-specific gene expression is not understood, and discrete enhancers required for gene regulation in the SAN have not been identified.

Objective:

To define the epigenetic profile of PCs using comparative ATAC-seq (assay for transposase-accessible chromatin with sequencing) and to identify novel enhancers involved in SAN gene regulation, development, and function.

Methods and Results:

We used ATAC-seq on sorted neonatal mouse SAN to compare regions of accessible chromatin in PCs and right atrial cardiomyocytes. PC-enriched assay for transposase-accessible chromatin peaks, representing candidate SAN regulatory elements, were located near established SAN genes and were enriched for distinct sets of TF (transcription factor) binding sites. Among several novel SAN enhancers that were experimentally validated using transgenic mice, we identified a 2.9-kb regulatory element at the
Isl1
locus that was active specifically in the cardiac inflow at embryonic day 8.5 and throughout later SAN development and maturation. Deletion of this enhancer from the genome of mice resulted in SAN hypoplasia and sinus arrhythmias. The mouse SAN enhancer also directed reporter activity to the inflow tract in developing zebrafish hearts, demonstrating deep conservation of its upstream regulatory network. Finally, single nucleotide polymorphisms in the human genome that occur near the region syntenic to the mouse enhancer exhibit significant associations with resting heart rate in human populations.

Conclusions:

(1) PCs have distinct regions of accessible chromatin that correlate with their gene expression profile and contain novel SAN enhancers, (2)
cis
-regulation of
Isl1
specifically in the SAN depends upon a conserved SAN enhancer that regulates PC development and SAN function, and (3) a corresponding human
ISL1
enhancer may regulate human SAN function.
Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells
Authors: Aherrahrou Redouane , Guo Liang , Nagraj V. Peter , Aguhob Aaron , Hinkle Jameson , Chen Lisa , Yuhl Soh Joon , Lue Dillon , Alencar Gabriel F. , Boltjes Arjan , van der Laan Sander W. , Farber Emily , Fuller Daniela , Anane-Wae Rita , Akingbesote Ngozi , Manichaikul Ani W. , Ma Lijiang , Kaikkonen Minna U. , Björkegren Johan L.M. , Önengüt-Gümüşcü Suna , Pasterkamp Gerard , Miller Clint L. , Owens Gary K. , Finn Aloke , Navab Mohamad , Fogelman Alan M. , Berliner Judith A. , Civelek Mete
Published: October 2020

Rationale:

Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Recent genome-wide association studies revealed 163 loci associated with CAD. However, the precise molecular mechanisms by which the majority of these loci increase CAD risk are not known. Vascular smooth muscle cells (VSMCs) are critical in the development of CAD. They can play either beneficial or detrimental roles in lesion pathogenesis, depending on the nature of their phenotypic changes.

Objective:

To identify genetic variants associated with atherosclerosis-relevant phenotypes in VSMCs.

Methods and Results:

We quantified 12 atherosclerosis-relevant phenotypes related to calcification, proliferation, and migration in VSMCs isolated from 151 multiethnic heart transplant donors. After genotyping and imputation, we performed association mapping using 6.3 million genetic variants. We demonstrated significant variations in calcification, proliferation, and migration. These phenotypes were not correlated with each other. We performed genome-wide association studies for 12 atherosclerosis-relevant phenotypes and identified 4 genome-wide significant loci associated with at least one VSMC phenotype. We overlapped the previously identified CAD loci with our data set and found nominally significant associations at 79 loci. One of them was the chromosome 1q41 locus, which harbors
MIA3
. The G allele of the lead risk single nucleotide polymorphism (SNP) rs67180937 was associated with lower VSMC
MIA3
expression and lower proliferation. Lentivirus-mediated silencing of MIA3 (melanoma inhibitory activity protein 3) in VSMCs resulted in lower proliferation, consistent with human genetics findings. Furthermore, we observed a significant reduction of MIA3 protein in VSMCs in thin fibrous caps of late-stage atherosclerotic plaques compared to early fibroatheroma with thick and protective fibrous caps in mice and humans.

Conclusions:

Our data demonstrate that genetic variants have significant influences on VSMC function relevant to the development of atherosclerosis. Furthermore, high
MIA3
expression may promote atheroprotective VSMC phenotypic transitions, including increased proliferation, which is essential in the formation or maintenance of a protective fibrous cap.
Acute Kidney Injury Sensitizes the Brain Vasculature to Ang II (Angiotensin II) Constriction via FGFBP1 (Fibroblast Growth Factor Binding Protein 1)
Authors: Zhao Liang , Cao Xiaoyun , Li Lingli , Wang Xiaohua , Wang Qin , Jiang Shan , Tang Chun , Zhou Suhan , Xu Nan , Cui Yu , Hu Weipeng , Fei Lingyan , Zheng Zhihua , Chen Limeng , Schmidt Marcel O. , Wei Qichun , Zhao Jingwei , Labes Robert , Patzak Andreas , Wilcox Christopher S. , Fu Xiaodong , Wellstein Anton , Lai En Yin
Published: October 2020

Acute kidney injury (AKI) causes multiple organ dysfunction. Here, we identify a possible mechanism that can drive brain vessel injury after AKI. We induced 30-minute bilateral renal ischemia-reperfusion injury in C57Bl/6 mice and isolated brain microvessels and macrovessels 24 hours or 1 week later to test their responses to vasoconstrictors and found that after AKI brain vessels were sensitized to Ang II (angiotensin II). Upregulation of FGF2 (fibroblast growth factor 2) and FGFBP1 (FGF binding protein 1) expression in both serum and kidney tissue after AKI suggested a potential contribution to the vascular sensitization. Administration of FGF2 and FGFBP1 proteins to isolated healthy brain vessels mimicked the sensitization to Ang II after AKI. Brain vessels in
Fgfbp1
−/−
AKI mice failed to induce Ang II sensitization. Complementary to this, systemic treatment with the clinically used FGF receptor kinase inhibitor BGJ398 (Infigratinib) reversed the AKI-induced brain vascular sensitization to Ang II. All these findings lead to the conclusion that FGFBP1 is especially necessary for AKI-mediated brain vascular sensitization to Ang II and inhibitors of FGFR pathway may be beneficial in preventing AKI-induced brain vessel injury.
Association Between Adherence to Quality Indicators and 7-Day In-Hospital Mortality After Acute Ischemic Stroke
Authors: Haas Kirsten , Rücker Viktoria , Hermanek Peter , Misselwitz Björn , Berger Klaus , Seidel Günter , Janssen Alfred , Rode Susanne , Burmeister Christoph , Matthis Christine , Koennecke Hans-Christian , Heuschmann Peter U. ,   on behalf of the German Stroke Register Study Group (ADSR)
Published: October 2020

Background and Purpose:

Quality indicators (QI) are an accepted tool to measure performance of hospitals in routine care. We investigated the association between quality of acute stroke care defined by overall adherence to evidence-based QI and early outcome in German acute care hospitals.

Methods:

Patients with ischemic stroke admitted to one of the hospitals cooperating within the ADSR (German Stroke Register Study Group) were analyzed. The ADSR is a voluntary network of 9 regional stroke registers monitoring quality of acute stroke care across 736 hospitals in Germany. Quality of stroke care was defined by adherence to 11 evidence-based indicators of early processes of stroke care. The correlation between overall adherence to QI with outcome was investigated by assessing the association between 7-day in-hospital mortality with the proportion of QI fulfilled from the total number of QI the individual patient was eligible for. Generalized linear mixed model analysis was performed adjusted for the variables age, sex, National Institutes of Health Stroke Scale and living will and as random effect for the variable hospital.

Results:

Between 2015 and 2016, 388 012 patients with ischemic stroke were reported (median age 76 years, 52.4% male). Adherence to distinct QI ranged between 41.0% (thrombolysis in eligible patients) and 95.2% (early physiotherapy). Seven-day in-hospital mortality was 3.4%. The overall proportion of QI fulfilled was median 90% (interquartile range, 75%–100%). In multivariable analysis, a linear association between overall adherence to QI and 7-day in-hospital-mortality was observed (odds ratio adherence <50% versus 100%, 12.7 [95% CI, 11.8–13.7];
P
<0.001).

Conclusions:

Higher quality of care measured by adherence to a set of evidence-based process QI for the early phase of stroke treatment was associated with lower in-hospital mortality.
Gastrointestinal Disorders and Risk of First-Ever Ischemic Stroke
Authors: Roth William H. , Cai Anna , Zhang Cenai , Chen Monica L. , Merkler Alexander E. , Kamel Hooman
Published: October 2020

Background and Purpose:

Recent studies suggest that alteration of the normal gut microbiome contributes to atherosclerotic burden and cardiovascular disease. While many gastrointestinal diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gastrointestinal diseases on subsequent cerebrovascular disease remains unknown. We conducted an exploratory analysis evaluating the relationship between gastrointestinal diseases and ischemic stroke.

Methods:

We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included only beneficiaries ≥66 years of age. We used previously validated diagnosis codes to ascertain our primary outcome of ischemic stroke. In an exploratory manner, we categorized gastrointestinal disorders by anatomic location, disease chronicity, and disease mechanism. We used Cox proportional hazards models to examine associations of gastrointestinal disorder categories and ischemic stroke with adjustment for demographics and established vascular risk factors.

Results:

Among a mean of 1 725 246 beneficiaries in each analysis, several categories of gastrointestinal disorders were associated with an increased risk of ischemic stroke after adjustment for established stroke risk factors. The most notable positive associations included disorders of the stomach (hazard ratio, 1.17 [95% CI, 1.15–1.19]) and functional (1.16 [95% CI, 1.15–1.17]), inflammatory (1.13 [95% CI, 1.12–1.15]), and infectious gastrointestinal disorders (1.13 [95% CI, 1.12–1.15]). In contrast, we found no associations with stroke for diseases of the anus and rectum (0.97 [95% CI, 0.94–1.00]) or neoplastic gastrointestinal disorders (0.97 [95% CI, 0.94–1.00]).

Conclusions:

In exploratory analyses, several categories of gastrointestinal disorders were associated with an increased risk of future ischemic stroke after adjustment for demographics and established stroke risk factors.
Experience on how to implement a preanalytical and POCT unit in Madrid’s IFEMA field hospital during this unprecedented COVID-19 emergency
Authors: Díaz–Garzón Jorge , Gómez Marta , Buño Antonio , Simón Manuela , Rodriguez-Fraga Olaia , Qasem Ana-Laila , Pascual Lydia , Moreno Isabel , Mora Roberto , Fernandez-Calle Pilar , Duque Marta , Crespo Gema , Oliver Paloma
Published: October 2020

To fight the virus SARS-CoV-2 spread to Europe from China and to give support to the collapsed public health system, the Spanish Health Authorities developed a field hospital located in the facilities of Madrid exhibition centre (IFEMA) to admit and treat patients diagnosed with SARS-CoV-2 infectious disease (COVID-19). The Department of Laboratory Medicine of La Paz University Hospital in Madrid (LMD-HULP) was designated to provide laboratory services. Due to the emergency, the IFEMA field hospital had to be prepared for patient admission in less than 1 week and the laboratory professionals had to collaborate in a multidisciplinary group to assure that resources were available to start on time. The LMD-HULP participated together with the managers in the design of the tests portfolio and the integration of the healthcare information systems (IS) (hospital IS, laboratory IS and POCT management system). Laboratorians developed a strategy to quickly train clinicians and nurses on test requests, sample collection procedures and management/handling of the POCT blood gas analyser both by written materials and training videos. The IFEMA´s preanalytical unit managed 3782 requests, and more than 11,000 samples from March 27th to April 30th. Furthermore, 1151 samples were measured by blood gas analysers. In conclusion, laboratory professionals must be resilient and have to respond timely in emergencies as this pandemic. The lab’s personnel selection, design and monitoring indicators to maintain and further improve the quality and value of laboratory services is crucial to support medical decision making and provide better patient care.
Test results comparison and sample stability study
Authors: Mandić Sanja , Mandić Dario , Šerić Vatroslav , Osvald Silvija , Lukić Maja , Horvat Vesna , Rolić Tara , Lukić Iva
Published: October 2020

Introduction: The aim was to evaluate the BD Barricor tubes by comparison with the BD Rapid Serum Tubes (RST) through measuring 25 analytes
and monitoring sample stability after 24 hours and 7 days.
Materials and methods: Samples of 52 patients from different hospital departments were examined. Blood was collected in BD RST and BD
Barricor tubes (Becton, Dickinson and Company, Franklin Lakes, USA). Analytes were measured by Beckman Coulter AU 480 (Beckman Coulter, Brea,
USA), Dimension EXL (Siemens Healthcare Diagnostics, Newark, USA) and ARCHITECT i2000SR (Abbott Diagnostics, Lake Forest, USA). Between-tube
comparison for each analyte was performed, along with testing analyte stability after storing samples at 4 °C.
Results: BD Barricor tubes showed unacceptable bias compared to BD RST tubes for potassium (K) (- 4.5%) and total protein (4.4%). Analyte stability
after 24 hours was acceptable in both tested tubes for most of analytes, except for glucose, aspartate aminotransferase (AST) and lactate dehydrogenase
(LD) in BD Barricor and free triiodothyronine in BD RST sample tubes. Analyte stability after 7 days was unacceptable for sodium, K, calcium,
creatine kinase isoenzyme MB, AST, LD and troponin I in both samples; additionally for glucose, alkaline phosphatase and albumin in BD Barricor.
Conclusion: All analytes, except K and total protein, can be measured interchangeably in BD RST and BD Barricor tubes, applying the same reference
intervals. For most of the analytes, sample re-analysis can be performed in both tubes after 24 hours and 7 days, although BD RST tubes show better
7-day analytes stability over BD Barricor tubes.
Comparison of a rapid immunochromatographic test with a chemiluminescence
immunoassay for detection of anti-SARS-CoV-2 IgM and IgG
Authors: Gambino Caterina Maria , Colomba Claudia , Ciaccio Marcello , Bivona Giulia , Agnello Luisa , Giglio Rosaria Vincenza , Lo Sasso Bruna
Published: October 2020

Introduction: The 2019 Coronavirus disease (COVID-19) has been characterized as a pandemic, representing a serious global public health emergency.
Serological tests have been proposed as reliable tools for detecting Coronavirus SARS-CoV-2 antibodies in infected patients, especially for
surveillance or epidemiological purposes. The aim of this study is to evaluate the agreement between the IgM/IgG rapid assays, based on lateral flow
immunochromatographic assay, and the fully automated 2019-nCoV IgM and IgG, based on chemiluminescence immunoassay.
Materials and methods: SARS-CoV-2 antibodies were measured with the BIOSYNEX COVID-19 BSS IgM/IgG test (BIOSYNEX, Illkirch-Graffenstaden,
France) and the MAGLUMI CLIA (IgM and IgG) (SNIBE – Shenzhen New Industries Biomedical Engineering, Shenzhen, China) in 70 serum samples
from patients with PCR-confirmed diagnosis. The strength of the agreement of the two methods was calculated by using the Cohen Kappa index.
Results: The results showed a good grade of concordance between the two immunoassays with a Cohen’s kappa coefficient of 0.71 (95%CI: 0.54-
0.87) for IgG SARS-CoV-2 antibodies and 0.70 (95%CI: 0.53-0.87) for IgM SARS-CoV-2 antibodies. In addition, the rapid assays BIOSYNEX COVID-19
BSS for detecting SARS-CoV-2 antibodies showed a positive likelihood ratio (LR) of 10.63 (95%CI: 2.79-40.57) for IgG and a LR of 6.79 (95%CI: 2.93-
15.69) for IgM.
Conclusion: Our results suggest that the immunochromatographic rapid IgM/IgG test and the chemiluminescence IgM and IgG immunoassay have
a good degree of concordance, suggesting that both could be considered as useful tools for epidemiologic surveillance.
Description of a new species of Smithophis Giri et al. 2019 (Serpentes: Colubridae: Natricinae) from Arunachal Pradesh, India
Authors: DAS ABHIJIT , DEEPAK V. , CAPTAIN ASHOK , WADE EDWARD O. Z. , GOWER DAVID J.
Published: October 2020

A new species of the natricine snake genus Smithophis Giri et al. 2019 is described based on three specimens collected from Arunachal Pradesh, India. An additional three referred specimens are documented. Smithophis arunachalensis sp. nov. differs from all known congeners by a combination of 4–5 (rarely 6) small scales around the eye (excluding labial scales), presence of temporal scales, and a distinctive colour pattern of a blackish dorsum and bright yellow venter that form a sharply-defined zigzag border. The new species is known only from ca. 100 km2 in Lower Dibang Valley and Changlang Districts in eastern Arunachal Pradesh. A revised key to the identification of the species of Smithophis is presented.
Examination of Aerosol-Induced Convective Invigoration Using Idealized Simulations
Authors: Cotton William R. , Walko Robert
Published: October 2020

Idealized large-eddy simulations (LESs) are performed of deep convective clouds over south Florida to examine the relative role of aerosol-induced condensational versus mixed-phase invigoration to convective intensity and rainfall. Aerosol concentrations and chemistry are represented by using output from the GEOS-Chem global atmospheric chemistry model run with and without anthropogenic aerosol sources. The results clearly show that higher aerosol concentrations result in enhanced precipitation, larger amounts of cloud liquid water content, enhanced updraft velocities during the latter part of the simulation, and a modest enhancement of the latent heating of condensation. Overall, our results are consistent with the concept that convective cloud invigoration is mainly due to condensational invigoration and not primarily to mixed-phase invigoration. Furthermore, our results suggest that condensational invigoration can result in appreciable precipitation enhancement of ordinary warm-based convective clouds such as are common in locations like south Florida.
Different Impacts of the East Asian Winter Monsoon on the Surface Air Temperature in North America during ENSO and Neutral ENSO Years
Authors: Ma Tianjiao , Chen Wen , Graf Hans-F. , Ding Shuoyi , Xu Peiqiang , Song Lei , Lan Xiaoqing
Published: October 2020

The present study investigates different impacts of the East Asian winter monsoon (EAWM) on surface air temperature (Ts) in North America (NA) during ENSO and neutral ENSO episodes. In neutral ENSO years, the EAWM shows a direct impact on the Ts anomalies in NA on an interannual time scale. Two Rossby wave packets appear over the Eurasian–western Pacific (upstream) and North Pacific–NA (downstream) regions associated with a strong EAWM. Further analysis suggests that the downstream wave packet is caused by reflection of the upstream wave packet over the subtropical western Pacific and amplified over the North Pacific. Also, the East Asian subtropical westerly jet stream (EAJS) is intensified in the central and downstream region over the central North Pacific. Hence, increased barotropic kinetic energy conversion and the interaction between transient eddies and the EAJS tend to maintain the circulation anomaly over the North Pacific. Therefore, a strong EAWM tends to result in warm Ts anomalies in northwestern NA via the downstream wave packet emanating from the central North Pacific toward NA. A weak EAWM tends to induce cold Ts anomalies in western-central NA with a smaller magnitude. However, in ENSO years, an anomalous EAJS is mainly confined over East Asia and does not extend into the central North Pacific. The results confirm that the EAWM has an indirect impact on the Ts anomalies in NA via a modulation of the tropical convection anomalies associated with ENSO. Our results indicate that, for seasonal prediction of Ts anomalies in NA, the influence of the EAWM should be taken into account. It produces different responses in neutral ENSO and in ENSO years.
Energy-saving control of long-range autonomous underwater vehicle vertical plane based on human simulating intelligent control method
Authors: Xu Hao , Zhang Guo-cheng , Sun Yu-shan , Pang Shuo
Published: October 2020

The long-range autonomous underwater vehicle is a new underwater vehicle with capability of stereoscopic observation of the ocean over a wide range of time series. This article proposed a novel control strategy for the long-range autonomous underwater vehicle considering the energy consumption. The vertical motion model of long-range autonomous underwater vehicle and the mathematical model of energy consumption of motion actuators are established in this article, and the maneuverability simulation experiments were carried out to analyze its motion and energy consumption characteristics. A hybrid controller based on human simulating intelligent control and S-plane control is designed. Considering the moment caused by the asymmetry of the hull in motion, an adaptive dynamic control allocation strategy is designed. Simulation experiments are conducted to demonstrate the performance of the scheme proposed.
An updated explanation of ancestral karyotype changes and reconstruction of evolutionary trajectories to form Camelina sativa chromosomes
Authors: Zhang Zhikang , Meng Fanbo , Sun Pengchuan , Yuan Jiaqing , Gong Ke , Liu Chao , Wang Weijie , Wang Xiyin
Published: October 2020

Background

Belonging to lineage I of Brassicaceae, Camelina sativa is formed by two hybridizations of three species (three sub-genomes). The three sub-genomes were diverged from a common ancestor, likely derived from lineage I (Ancestral Crucifer karyotype, ACK). The karyotype evolutionary trajectories of the C. sativa chromosomes are currently unknown. Here, we managed to adopt a telomere-centric theory proposed previously to explain the karyotype evolution in C. sativa.

Results

By characterizing the homology between A. lyrata and C. sativa chromosomes, we inferred ancestral diploid karyotype of C. sativa (ADK), including 7 ancestral chromosomes, and reconstructed the evolutionary trajectories leading to the formation of extant C. sativa genome. The process involved 2 chromosome fusions. We found that sub-genomes Cs-G1 and Cs-G2 may share a closer common ancestor than Cs-G3. Together with other lines of evidence from Arabidopsis, we propose that the Brassicaceae plants, even the eudicots, follow a chromosome fusion mechanism favoring end-end joining of different chromosomes, rather than a mechanism favoring the formation circular chromosomes and nested chromosome fusion preferred by the monocots.

Conclusions

The present work will contribute to understanding the formation of C. sativa chromosomes, providing insight into Brassicaceae karyotype evolution.
Comparative transcriptome analysis reveals that PCK1 is a potential gene affecting IMF deposition in buffalo
Authors: Huang Jieping , Feng Xue , Zhu Ruirui , Guo Duo , Wei Yutong , Cao Xiaodan , Ma Yun , Shi Deshun
Published: October 2020

Background

In China, although buffaloes are abundant, beef is mainly obtained from cattle, and this preference is mainly attributed to the low intramuscular fat (IMF) content of buffalo. Genetic factors are an important driver that affects IMF deposition.

Results

To reveal the intrinsic factors responsible for the low IMF content of buffalo, mRNA expression patterns in muscle and adipose tissue between buffalo and cattle were characterized by RNA sequencing analysis. The IMF content in Nanyang cattle was higher than that in Xinyang buffalo. A total of 1566 mRNAs expressed in adipose tissue showed differential expression between the longissimus dorsi muscles of buffalo and cattle. Functional annotation suggested a difference in the glycolysis/gluconeogenesis pathway between the two species. The results of RT-qPCR analysis and gain-of-function experiments confirmed the positive association between the IMF content and phosphoenolpyruvate carboxykinase 1 (PCK1) expression in buffalo. In both mouse C2C12 cells and cultured bovine myocytes, the activity of the PCK1 promoter in buffalo is lower than that in cattle. However, in mouse 3T3-L1 adipocytes and cultured bovine adipocytes, the activity of PCK1 in buffalo promoter is higher than that in cattle.

Conclusions

These results indicate the important role of PCK1 in buffalo IMF deposition and illustrate the differences between buffalo and cattle promoter activity that drive PCK1 expression. This research helps to establish a foundation for further studies investigating IMF deposition in buffalo.
Identification of fungi in Tunisian olive orchards: characterization and biological control potential
Authors: Gharsallah Houda , Ksentini Ines , Naayma Sourour , Hadj Taieb Karama , Abdelhedi Nour , Schuster Christina , Triki Mohamed Ali , Ksantini Mohieddine , Leclerque Andreas
Published: October 2020

Background

Olive production is the main agricultural activity in Tunisia. The diversity of fungi was explored in two different olive groves located in two distant geographical zones in Sfax (Tunisia) with different management practices.

Results

Fungal isolation was made from soil and the major olive tree pests, namely the Olive fly,Bactrocera oleaeGmelin (Diptera: Tephritidae), and the Olive psyllid,Euphyllura olivinaCosta (Homoptera: Psyllidae). A total of 34 fungal isolates were identified according to their phenotypic, genotypic, biochemical and biological activities. Twenty fungal species were identified belonging to six different genera (Alternaria,Aspergillus,Cladosporium,Fusarium,LecanicilliumandPenicillium) by the analysis of their ITS1–5.8S–ITS2 ribosomal DNA region. Different bioassays performed in this work revealed that 25/34 (73.5%) of the identified fungal isolates showed an entomopathogenic and/or antagonistic activity, 9/34 (26.5%) of them displayed phytopathogenic features.

Conclusions

Fungal species that showed entomopathogenic and/or antagonistic potentialities and that are non-phytopathogenic, (17/34; 50%) of our fungal isolates, could be explored for olive protection against fungal diseases and pests, and might have a future application as biocontrol agents.