bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of Levamisole treatment in clinical presentations of non-hospitalized patients with COVID-19: a double-blind, randomized, controlled trial
Authors: Roostaei Firozabad Amirreza , Meybodi Zohreh Akhoundi , Mousavinasab Seyed Ruhollah , Sahebnasagh Adeleh , Jelodar Mohsen Gholinataj , Karimzadeh Iman , Habtemariam Solomon , Saghafi Fatemeh 
Published: March 2021

Abstract
Background
Levamisole has shown clinical benefits in the management of COVID-19 via its immunomodulatory effect. However, the exact role of Levamisole effect in clinical status of COVID-19 patients is unknown. We aimed to evaluate the efficacy of Levamisole on clinical status of patients with COVID-19 during their course of the disease.

Methods
This prospective, double-blind, randomized controlled clinical trial was performed in adult patients with mild to moderate COVID-19 (room-air oxygen saturation > 94%) from late April 2020 to mid-August 2020. Patients were randomly assigned to receive a 3-day course of Levamisole or placebo in combination with routine standard of care.

Results
With 25 patients in each arm, 50 patients with COVID-19 were enrolled in the study. Most of the study participants were men (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution when compared to the placebo group (P-value = 0.034 and 0.005, respectively). Moreover, there was significant differences between the two groups in dyspnea at follow-up intervals of 7 (P-value = 0.015) and 14 (P-value = 0.010) days after receiving the interventions. However, no significant difference in fever status was observed on days 1, 3, 7, and 14 in both groups (P-value > 0.05).

Conclusion
The results of the current study suggest that Levamisole may improve most of clinical status of patients with COVID-19. The patients receiving Levamisole had significantly better chance of clinical status including cough and dyspnea on day 14 when compared to the placebo. However, the effect-size of this finding has uncertain clinical importance.

Trial registration
The trial was registered as IRCT20190810044500N7 (19/09/2020).
Winter is coming: the future of cryopreservation
Authors: Bojic Sanja , Murray Alex , Bentley Barry L. , Spindler Ralf , Pawlik Piotr , Cordeiro José L. , Bauer Roman , de Magalhães João Pedro 
Published: March 2021

AbstractThe preservative effects of low temperature on biological materials have been long recognised, and cryopreservation is now widely used in biomedicine, including in organ transplantation, regenerative medicine and drug discovery. The lack of organs for transplantation constitutes a major medical challenge, stemming largely from the inability to preserve donated organs until a suitable recipient is found. Here, we review the latest cryopreservation methods and applications. We describe the main challenges—scaling up to large volumes and complex tissues, preventing ice formation and mitigating cryoprotectant toxicity—discuss advantages and disadvantages of current methods and outline prospects for the future of the field.
Neuronal cell-based high-throughput screen for enhancers of mitochondrial function reveals luteolin as a modulator of mitochondria-endoplasmic reticulum coupling
Authors: Naia Luana , Pinho Catarina M. , Dentoni Giacomo , Liu Jianping , Leal Nuno Santos , Ferreira Duarte M. S. , Schreiner Bernadette , Filadi Riccardo , Fão Lígia , Connolly Niamh M. C. , Forsell Pontus , Nordvall Gunnar , Shimozawa Makoto , Greotti Elisa , Basso Emy , Theurey Pierre , Gioran Anna , Joselin Alvin , Arsenian-Henriksson Marie , Nilsson Per , Rego A. Cristina , Ruas Jorge L. , Park David , Bano Daniele , Pizzo Paola , Prehn Jochen H. M. , Ankarcrona Maria 
Published: March 2021

Abstract
Background
Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with promising therapeutic potential.

Results
Using differentiated human neuroblastoma cells, we screened 1200 FDA-approved compounds and identified 61 molecules that significantly increased cellular ATP without any cytotoxic effect. Following dose response curve-dependent selection, we identified the flavonoid luteolin as a primary hit. Further validation in neuronal models indicated that luteolin increased mitochondrial respiration in primary neurons, despite not affecting mitochondrial mass, structure, or mitochondria-derived reactive oxygen species. However, we found that luteolin increased contacts between mitochondria and endoplasmic reticulum (ER), contributing to increased mitochondrial calcium (Ca2+) and Ca2+-dependent pyruvate dehydrogenase activity. This signaling pathway likely contributed to the observed effect of luteolin on enhanced mitochondrial complexes I and II activities. Importantly, we observed that increased mitochondrial functions were dependent on the activity of ER Ca2+-releasing channels inositol 1,4,5-trisphosphate receptors (IP3Rs) both in neurons and in isolated synaptosomes. Additionally, luteolin treatment improved mitochondrial and locomotory activities in primary neurons and Caenorhabditis elegans expressing an expanded polyglutamine tract of the huntingtin protein.

Conclusion
We provide a new screening platform for drug discovery validated in vitro and ex vivo. In addition, we describe a novel mechanism through which luteolin modulates mitochondrial activity in neuronal models with potential therapeutic validity for treatment of a variety of human diseases.
Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension
Authors: Naguib Yahya M. , Samaka Rehab M. , Rizk Mohamed S. , Ameen Omnia , Motawea Shaimaa M. 
Published: March 2021

AbstractBackgroundThe prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model.MethodsThirty male Wistar rats weighing 150–200 g were equally divided into: 1—Control group (fed normal laboratory diet for 24 weeks), 2—Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3—Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies.ResultsHigh fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions.ConclusionAdipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.
Delivery of cancer therapies by synthetic and bio-inspired nanovectors
Authors: Briolay Tina , Petithomme Tacien , Fouet Morgane , Nguyen-Pham Nelly , Blanquart Christophe , Boisgerault Nicolas 
Published: March 2021

Abstract
Background
As a complement to the clinical development of new anticancer molecules, innovations in therapeutic vectorization aim at solving issues related to tumor specificity and associated toxicities. Nanomedicine is a rapidly evolving field that offers various solutions to increase clinical efficacy and safety.

Main
Here are presented the recent advances for different types of nanovectors of chemical and biological nature, to identify the best suited for translational research projects. These nanovectors include different types of chemically engineered nanoparticles that now come in many different flavors of ‘smart’ drug delivery systems. Alternatives with enhanced biocompatibility and a better adaptability to new types of therapeutic molecules are the cell-derived extracellular vesicles and micro-organism-derived oncolytic viruses, virus-like particles and bacterial minicells. In the first part of the review, we describe their main physical, chemical and biological properties and their potential for personalized modifications. The second part focuses on presenting the recent literature on the use of the different families of nanovectors to deliver anticancer molecules for chemotherapy, radiotherapy, nucleic acid-based therapy, modulation of the tumor microenvironment and immunotherapy.

Conclusion
This review will help the readers to better appreciate the complexity of available nanovectors and to identify the most fitting “type” for efficient and specific delivery of diverse anticancer therapies.
Microglia activated by microbial neuraminidase contributes to ependymal cell death
Authors: Fernández-Arjona María del Mar , León-Rodríguez Ana , López-Ávalos María Dolores , Grondona Jesús M. 
Published: March 2021

AbstractThe administration of microbial neuraminidase into the brain ventricular cavities of rodents represents a model of acute aseptic neuroinflammation. Ependymal cell death and hydrocephalus are unique features of this model. Here we demonstrate that activated microglia participates in ependymal cell death. Co-cultures of pure microglia with ependymal cells (both obtained from rats) were performed, and neuraminidase or lipopolysaccharide were used to activate microglia. Ependymal cell viability was unaltered in the absence of microglia or inflammatory stimulus (neuraminidase or lipopolysaccharide). The constitutive expression by ependymal cells of receptors for cytokines released by activated microglia, such as IL-1β, was demonstrated by qPCR. Besides, neuraminidase induced the overexpression of both receptors in ventricular wall explants. Finally, ependymal viability was evaluated in the presence of functional blocking antibodies against IL-1β and TNFα. In the co-culture setting, an IL-1β blocking antibody prevented ependymal cell death, while TNFα antibody did not. These results suggest that activated microglia are involved in the ependymal damage that occurs after the administration of neuraminidase in the ventricular cavities, and points to IL-1β as possible mediator of such effect. The relevance of these results lies in the fact that brain infections caused by neuraminidase-bearing pathogens are frequently associated to ependymal death and hydrocephalus.
Prevalence of suicidal ideation and attempted suicide in the general population of Ethiopia: a systematic review and meta-analysis
Authors: Bifftu Berhanu Boru , Tiruneh Bewket Tadesse , Dachew Berihun Assefa , Guracho Yonas Deressa 
Published: March 2021

Abstract
Background
In Ethiopia, in spite of the high burden of suicide related-adverse effect, substantial variability in the reported prevalence of individual studies about suicidal ideation and attempted suicide; there is no national level epidemiological evidence. Thus, the present study aimed to determine the pooled prevalence of suicide ideation and suicidal attempt in the general population.

Methods
We followed the PRISMA Guidelines to report the results of the finding. Databases including: PubMed/Medline, SCOPUS, CINAHL (EBSCOhost), African Journal Online (AJOL) and African Indexed Medicus (AIM) were searched. Heterogeneity was assessed by Cochrane chi-square (χ2) and quantified by I2 statistics test. Sensitivity test and subgroup analysis performed. Publication bias was tested by funnel plots and Egger’s test. Effect size was calculated by random effects model.

Results
A total of 12 studies for suicidal ideation and 10 studies for attempted suicide were included in the study. The prevalence of suicidal ideation and attempted suicide were ranged from 1 to 55% and 0.6% to 14% respectively. The 12-month pooled prevalence of suicidal ideation and suicidal attempt were 9% (5–16%), I2 = 99.64%, p < 0.001 and 4% (1–8%), I2 = 98.11%, p < 0.001] respectively. The lifetime pooled prevalence of attempted suicide was found to be 4% (3–6%). We found evidence of significant heterogeneity for suicidal ideation [I2 = 99.64%, p < 0.001] and attempted suicide [I2 = 98.11%, p < 0.001]. The subgroup analysis could not identified source of heterogeneity. The sensitivity analysis showed that none of the point estimates was outside of the overall 95%CI for suicidal ideation and attempted suicide. No evidence of publication bias from the visual inspection of the funnel plot for suicidal ideation and [Egger’s test (P = 0.174)] and attempted suicide [Egger’s test (P = 0.318)].

Conclusion
High prevalence of suicidal ideation and attempted suicide were observed in the general population of Ethiopia. These suggest the need of strengthening the awareness of suicidal behaviours and evaluate the effectiveness of the national health strategy in addressing the issues of suicidal behaviours.
Pediatric routine vaccinations in the COVID 19 lockdown period: the survey of the Italian Pediatric Society
Authors: Russo Rocco , Bozzola Elena , Palma Paolo , Corsello Giovanni , Villani Alberto 
Published: March 2021

Abstract
Background
COVID-19 pandemic was responsible for disrupting routine immunization activities all over the world. Aim of the study was to investigate the reduced adherence to the national children vaccination schedule during the lockdown period in Italy.

Materials and methods
Through social channels, the Italian Pediatric Society conducted a survey among Italian families on children vaccination during lockdown period.

Results
In the study period, 1474 responders were collected. More than one third (34%) of them skipped the vaccine appointment as they were afraid of SARS-CoV-2-virus (44%), vaccination services postponed the appointment (42%) or was closed to public (13%).

Discussion
Reduction in routine immunization coverage may represent a serious life-threating problem for unvaccinated or under-vaccinated children.

Conclusions
Information on national and local preventive measures including physical distancing, handwashing, and proper coughing/sneezing hygiene should be spread among families in order to contrast vaccine hesitancy and maintain adequate coverage levels during COVID19 pandemic period.
CACTUS: integrating clonal architecture with genomic clustering and transcriptome profiling of single tumor cells
Authors: Shafighi Shadi Darvish , Kiełbasa Szymon M. , Sepúlveda-Yáñez Julieta , Monajemi Ramin , Cats Davy , Mei Hailiang , Menafra Roberta , Kloet Susan , Veelken Hendrik , van Bergen Cornelis A.M. , Szczurek Ewa 
Published: March 2021

Abstract
Background
Drawing genotype-to-phenotype maps in tumors is of paramount importance for understanding tumor heterogeneity. Assignment of single cells to their tumor clones of origin can be approached by matching the genotypes of the clones to the mutations found in RNA sequencing of the cells. The confidence of the cell-to-clone mapping can be increased by accounting for additional measurements. Follicular lymphoma, a malignancy of mature B cells that continuously acquire mutations in parallel in the exome and in B cell receptor loci, presents a unique opportunity to join exome-derived mutations with B cell receptor sequences as independent sources of evidence for clonal evolution.

Methods
Here, we propose CACTUS, a probabilistic model that leverages the information from an independent genomic clustering of cells and exploits the scarce single cell RNA sequencing data to map single cells to given imperfect genotypes of tumor clones.

Results
We apply CACTUS to two follicular lymphoma patient samples, integrating three measurements: whole exome, single-cell RNA, and B cell receptor sequencing. CACTUS outperforms a predecessor model by confidently assigning cells and B cell receptor-based clusters to the tumor clones.

Conclusions
The integration of independent measurements increases model certainty and is the key to improving model performance in the challenging task of charting the genotype-to-phenotype maps in tumors. CACTUS opens the avenue to study the functional implications of tumor heterogeneity, and origins of resistance to targeted therapies. CACTUS is written in R and source code, along with all supporting files, are available on GitHub (https://github.com/LUMC/CACTUS).
Diverting less urgent utilizers of emergency medical services to primary care: is it feasible? Patient and morbidity characteristics from a cross-sectional multicenter study of self-referring respiratory emergency department consulters
Authors: Holzinger Felix , Oslislo Sarah , Resendiz Cantu Rebecca , Möckel Martin , Heintze Christoph 
Published: March 2021

Abstract
Objective
Diversion of less urgent emergency medical services (EMS) callers to alternative primary care (PC) is much debated. Using data from the EMACROSS survey of respiratory ED patients, we aimed to characterize self-referred EMS patients, compare these with non-EMS patients, and assess scope and acceptability of a potential redirection to alternative PC.

Results
Of n = 292 self-referred patients, n = 99 were transported by EMS. Compared to non-EMS patients, these were older, triaged more urgently and arrived out-of-hours more frequently. The share of chronically and severely ill patients was greater. Out-of-hours ED visit, presence of a chronic pulmonary condition as well as a hospital diagnosis of respiratory failure were identified as determinants of EMS utilization in a logistic model, while consultation for access and quality motives as well as migrant status decreased the probability. EMS-transported lower urgency outpatients visiting during regular physicians’ hours were defined as potential PC cases and evaluated descriptively (n = 9). As a third was medically complex and potentially less suitable for PC, redirection potential could be estimated at only 6% of EMS cases. This would be reduced to 2% if considering patients’ judgment concerning the appropriate setting. Overall, the scope for PC diversion of respiratory EMS patients seems limited.
16S rRNA sequencing of samples from universal stool bank donors
Authors: Santiago Marina , Olesen Scott W. 
Published: March 2021

Abstract
Objectives
Universal stool banks provide stool to physicians for use in treating recurrent Clostridioides difficile infection via fecal microbiota transplantation. Stool donors providing the material are rigorously screened for diseases and disorders with a potential microbiome etiology, and they are likely healthier than the controls in most microbiome datasets. 16S rRNA sequencing was performed on samples from a selection of stool donors at a large stool bank, OpenBiome, to characterize their gut microbial community and to compare samples across different timepoints and sequencing runs.

Data description
16S rRNA sequencing was performed on 200 samples derived from 170 unique stool donations from 86 unique donors. Samples were sequenced on 11 different sequencing runs. We are making this data available because rigorously screened, likely very healthy stool donors may be useful for characterizing and understanding microbial community differences across different populations and will help shed light into the how the microbiome community promotes health and disease.
Seronegative limbic encephalitis manifesting as subacute amnestic syndrome: a case report and review of the literature
Authors: Ismail Ismail Ibrahim , Alnaser Fahad , Al-Hashel Jasem Y. 
Published: March 2021

Abstract
Background
Limbic encephalitis (LE), a variant of autoimmune encephalitis, is inflammation of the limbic system of the brain. The disorder presents with subacute impairment of short-term memory, psychiatric manifestations, confusion and seizures. “Seronegative LE” is a challenging diagnosis in the absence of well-characterized autoantibodies.

Case presentation
A 33-year-old Kuwaiti woman with no relevant past history presented with subacute progressive amnesia of 6-month duration. Magnetic resonance imaging (MRI) showed bilateral hyperintensity of the limbic structures. An extensive workup of the blood and cerebrospinal fluid (CSF) failed to identify paraneoplastic or autoimmune antibodies. The diagnosis of seronegative LE was made, and immunotherapy was initiated, with improvement in cognitive function.

Conclusion
Seronegative LE is a challenging diagnosis. Inability to detect autoantibodies, especially early in the disease course, should not rule out the diagnosis of autoimmune encephalitis. Early diagnosis and treatment with immunotherapy may prevent irreversible brain damage.
Analysis of the effects of related fingerprints on molecular similarity using an eigenvalue entropy approach
Authors: Kuwahara Hiroyuki , Gao Xin 
Published: March 2021

AbstractTwo-dimensional (2D) chemical fingerprints are widely used as binary features for the quantification of structural similarity of chemical compounds, which is an important step in similarity-based virtual screening (VS). Here, using an eigenvalue-based entropy approach, we identified 2D fingerprints with little to no contribution to shaping the eigenvalue distribution of the feature matrix as related ones and examined the degree to which these related 2D fingerprints influenced molecular similarity scores calculated with the Tanimoto coefficient. Our analysis identified many related fingerprints in publicly available fingerprint schemes and showed that their presence in the feature set could have substantial effects on the similarity scores and bias the outcome of molecular similarity analysis. Our results have implication in the optimal selection of 2D fingerprints for compound similarity analysis and the identification of potential hits for compounds with target biological activity in VS.
Negative selection—a new performance measure for automated order execution
Authors: Kumaresan Miles , Krejić Nataša , Lončar Sanja 
Published: March 2021

AbstractAutomated Order Execution is the dominant way of trading at stock markets. Performance of numerous execution algorithms is measured through slippage from some benchmark. But measuring true slippage in algorithmic execution is a difficult task since the execution as well as benchmarks are function of market activity. In this paper, we propose a new performance measure for execution algorithms. The measure, named Negative Selection, takes a posterior look at the trading window and allows us to determine what would have been the optimal order placement if we knew in advance, before the actual trading, the complete market information during the trading window. We define the performance measure as the difference between the hypothetical optimal trading position and the actual execution. This difference is calculated taking into account all prices and traded quantities within the considered time window. Thus, we are capturing the impact caused by our own trading as a cost that affects all trades. Properties of Negative Selection, which make it well defined and objective are discussed. Some empirical results on real trade data are presented.