bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy
Authors: De Waele Jorrit , Verhezen Tias , van der Heijden Sanne , Berneman Zwi N. , Peeters Marc , Lardon Filip , Wouters An , Smits Evelien L. J. M. 
Published: June 2021

AbstractImmunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological complexities surrounding glioblastoma, lymphocytes that infiltrate the brain to develop durable immunity with memory will be key. Polyinosinic:polycytidylic acid, or poly(I:C), and its derivative poly-ICLC could serve as a priming or boosting therapy to unleash lymphocytes and other factors in the (immuno)therapeutic armory against glioblastoma. Here, we present a systematic review on the effects and efficacy of poly(I:C)/poly-ICLC for glioblastoma treatment, ranging from preclinical work on cellular and murine glioblastoma models to reported and ongoing clinical studies. MEDLINE was searched until 15 May 2021 to identify preclinical (glioblastoma cells, murine models) and clinical studies that investigated poly(I:C) or poly-ICLC in glioblastoma. A systematic review approach was conducted according to PRISMA guidelines.ClinicalTrials.govwas queried for ongoing clinical studies. Direct pro-tumorigenic effects of poly(I:C) on glioblastoma cells have not been described. On the contrary, poly(I:C) changes the immunological profile of glioblastoma cells and can also kill them directly. In murine glioblastoma models, poly(I:C) has shown therapeutic relevance as an adjuvant therapy to several treatment modalities, including vaccination and immune checkpoint blockade. Clinically, mostly as an adjuvant to dendritic cell or peptide vaccines, poly-ICLC has been demonstrated to be safe and capable of eliciting immunological activity to boost therapeutic responses. Poly-ICLC could be a valuable tool to enhance immunotherapeutic approaches for glioblastoma. We conclude by proposing several promising combination strategies that might advance glioblastoma immunotherapy and discuss key pre-clinical aspects to improve clinical translation.
The Retornus-2 study: impact of respiratory muscle training in subacute stroke patients with dysphagia, study protocol of a double-blind randomized controlled trial
Authors: Guillen-Sola A. , Messaggi-Sartor M. , Ramírez-Fuentes C. , Marco E. , Duarte E. 
Published: June 2021

Abstract
Background
Stroke can lead to varying degrees of oropharyngeal dysphagia, respiratory muscle dysfunction and even increase medical complications such as aspiration, malnutrition and death. Recent studies suggest that inspiratory and expiratory respiratory muscle training (IEMT) can improve swallowing efficacy and may reduce aspiration events. The main purpose of this study is to examine whether an 8-week IEMT programme can improve respiratory muscle strength and swallow dysfunction severity in subacute stroke patients with dysphagia.

Methods
Retornus-2 is a two-arm, prospectively registered, randomized controlled study with blinded assessors and the participation of fifty individuals who have suffered a stroke. The intervention group undergoes IEMT training consisting of 5 sets of 10 repetitions, three times a day for 8 weeks. Training loads increase weekly. The control group undergoes a sham-IEMT protocol. The primary outcome examines the efficacy of the IEMT protocol to increase respiratory muscle strength and reduce dysphagia severity. The secondary outcome assesses the longitudinal impact of dysphagia on body composition and nutritional assessment over a 6-month follow-up.

Discussion
IEMT induces an improvement in respiratory muscle strength and might be associated with relevant benefits in dysphagia patterns, as well as a reduction in the number of aspiration events confirmed by videofluoroscopy or fiberoptic endoscopic evaluation of swallowing. The description of the impact of swallowing impairment on nutritional status will help develop new strategies to face this known side-effect.

Trial registration
Clinicaltrials.gov NCT03021252. Registered on 10 January 2017. https://clinicaltrials.gov/ct2/results?cond=retornus+2&term=&cntry=ES&state=&city=&dist=
WHO trial Registration data set: Due to heavy traffic generated by the COVID-19 outbreak, the ICTRP Search Portal does not respond. The portal recommends other registries such as clinicaltrials.gov. Protocol version: RETORNUS 2_ PROTOCOL_2.
Exploiting prunability for person re-identification
Authors: Masson Hugo , Bhuiyan Amran , Nguyen-Meidine Le Thanh , Javan Mehrsan , Siva Parthipan , Ayed Ismail Ben , Granger Eric 
Published: June 2021

AbstractRecent years have witnessed a substantial increase in the deep learning (DL) architectures proposed for visual recognition tasks like person re-identification, where individuals must be recognized over multiple distributed cameras. Although these architectures have greatly improved the state-of-the-art accuracy, the computational complexity of the convolutional neural networks (CNNs) commonly used for feature extraction remains an issue, hindering their deployment on platforms with limited resources, or in applications with real-time constraints. There is an obvious advantage to accelerating and compressing DL models without significantly decreasing their accuracy. However, the source (pruning) domain differs from operational (target) domains, and the domain shift between image data captured with different non-overlapping camera viewpoints leads to lower recognition accuracy. In this paper, we investigate the prunability of these architectures under different design scenarios. This paper first revisits pruning techniques that are suitable for reducing the computational complexity of deep CNN networks applied to person re-identification. Then, these techniques are analyzed according to their pruning criteria and strategy and according to different scenarios for exploiting pruning methods to fine-tuning networks to target domains. Experimental results obtained using DL models with ResNet feature extractors, and multiple benchmarks re-identification datasets, indicate that pruning can considerably reduce network complexity while maintaining a high level of accuracy. In scenarios where pruning is performed with large pretraining or fine-tuning datasets, the number of FLOPS required by ResNet architectures is reduced by half, while maintaining a comparable rank-1 accuracy (within 1% of the original model). Pruning while training a larger CNNs can also provide a significantly better performance than fine-tuning smaller ones.
Cognitive interventions in children and adolescents from low socioeconomic status backgrounds: a systematic review protocol of randomized controlled trials
Authors: Company-Córdoba Rosalba , Sianes Antonio , Simpson Ian Craig , Ibáñez-Alfonso Joaquín A. 
Published: June 2021

Abstract
Background
Many studies have evaluated the effects that a lack of resources has in children’s physical and cognitive development. Although there are reviews that have focused on applied interventions from different perspectives, there is still a need for a comprehensive review of what has been attempted with these children from the cognitive intervention field. The aim of this paper is to present a protocol for a systematic review collecting randomized controlled trials (RCTs) studies whose purpose was to enhance cognitive development through the implementation of cognitive interventions in children and adolescents (< 18 years old) from low socioeconomic Status (SES) settings.

Methods
The following databases will be searched: Web of Science (WoS core collection), PsycINFO, Cochrane Central Register of Controlled Trial, ERIC, PubMed, ICTRP and Opengrey Register (System for Information of Grey Literature in Europe). Searches will be adapted for each database. Additionally, the reference list of articles included in the review will also be searched. As part of this process, two reviewers will determine, independently, the suitability of each article taking into account predefined inclusion/exclusion criteria. Pertinent data will then be extracted, including sample characteristics, specifics of the intervention, and outcomes, as well as follow-up measures. Internal validity will be assessed using the Cochrane Risk of Bias Tool. A quantitative synthesis of results will be conducted using a meta-analysis. However, if a meta-analysis is difficult to implement due to the diversity of the studies (for example, in terms of measures used to estimate the effect size, intervention types, outcomes, etc.), the technique synthesis without meta-analysis (SWiM) will be used. A description of outcome measures will be provided, as measured by validated neuropsychological instruments of any cognitive function.

Discussion
The systematic review will offer a framework based on evidence to organisations, institutions, and experts who want to implement or promote interventions aimed at enhancing cognitive domains in children and adolescents who live in disadvantaged contexts.

Systematic review registration
This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 16 March 2020 (registration number: CDR42020150238).
Stable finite difference method for fractional reaction–diffusion equations by compact implicit integration factor methods
Authors: Zhang Rongpei , Li Mingjun , Chen Bo , Zhang Liwei 
Published: June 2021

AbstractIn this paper we propose a stable finite difference method to solve the fractional reaction–diffusion systems in a two-dimensional domain. The space discretization is implemented by the weighted shifted Grünwald difference (WSGD) which results in a stiff system of nonlinear ordinary differential equations (ODEs). This system of ordinary differential equations is solved by an efficient compact implicit integration factor (cIIF) method. The stability of the second order cIIF scheme is proved in the discrete $L^{2}$

L
2

-norm. We also prove the second-order convergence of the proposed scheme. Numerical examples are given to demonstrate the accuracy, efficiency, and robustness of the method.
Effects of floods on macroinvertebrate communities in the Zarin Gol River of northern Iran: implications for water quality monitoring and biological assessment
Authors: Gholizadeh Mohammad 
Published: June 2021

Abstract
Background
The timing, magnitude, and duration of extreme hydrological disasters have the potential to threaten the species diversity and river habitats. On August 8, 2014, and August 19, 2017, disastrous floods struck mountainous regions of Iran’s Zarin Gol River basin. Macroinvertebrate communities were studied at seven upstreams prior to the floods in June 2014 and 2017 and after the floods in September 2014 and 2017 and 9 months after the second flood in June 2018. The effects of floods on macroinvertebrate communities, recovery rate of macroinvertebrate community resilience and influencing factors were investigated.

Results
Despite the fact that extreme floods were the only reason of the disruption, the effects of biological water quality assessment metrics after the disaster were comparable to those of heavily polluted waters. Biological indicators revealed that the communities were unaffected prior to the floods, and the water quality remained within acceptable limits. Following the disasters, the density of macroinvertebrates declined, and biological indicators demonstrated the severe depletion of water quality. Community indicators (species richness, percent model affinity (PMA), and Ephemeroptera, Plecoptera, and Trichoptera (EPT) richness) rebounded after 9 months (June 2018), demonstrating that Zarin Gol River’s macroinvertebrate communities could recover even after the severe impact of the floods. As a result, macroinvertebrate samples taken from flood-affected areas revealed that extreme flooding, rather than a decrease in water quality, causes a loss of diversity and abundance.

Conclusion
Because of shifts in hydrological regimes in streams around the world, understanding the short-term impacts of strong flooding and the comparatively quick recovery of macroinvertebrate ecosystems has important consequences for bio-assessment programs after severe floods.
Development of an unannounced standardized patient protocol to evaluate opioid use disorder treatment in pregnancy for American Indian and rural communities
Authors: Kelley A. Taylor , Smid Marcela C. , Baylis Jacob D. , Charron Elizabeth , Binns-Calvey Amy E. , Archer Shayla , Weiner Saul J. , Begaye Lori Jo , Cochran Gerald 
Published: June 2021

Abstract
Background
Opioid use disorder (OUD) disproportionately impacts rural and American Indian communities and has quadrupled among pregnant individuals nationwide in the past two decades. Yet, limited data are available about access and quality of care available to pregnant individuals in rural areas, particularly among American Indians (AIs). Unannounced standardized patients (USPs), or “secret shoppers” with standardized characteristics, have been used to assess healthcare access and quality when outcomes cannot be measured by conventional methods or when differences may exist between actual versus reported care. While the USP approach has shown benefit in evaluating primary care and select specialties, its use to date for OUD and pregnancy is very limited.

Methods
We used literature review, current practice guidelines for perinatal OUD management, and stakeholder engagement to design a novel USP protocol to assess healthcare access and quality for OUD in pregnancy. We developed two USP profiles—one white and one AI—to reflect our target study area consisting of three rural, predominantly white and AI US counties. We partnered with a local community health center network providing care to a large AI population to define six priority outcomes for evaluation: (1) OUD treatment knowledge among clinical staff answering telephones; (2) primary care clinic facilitation and provision of prenatal care and buprenorphine treatment; (3) appropriate completion of evidence-based screening, symptom assessment, and initial steps in management; (4) appropriate completion of risk factor screening/probing about individual circumstances that may affect care; (5) patient-directed tone, stigma, and professionalism by clinic staff; and (6) disparities in care between whites and American Indians.

Discussion
The development of this USP protocol tailored to a specific environment and high-risk patient population establishes an innovative approach to evaluate healthcare access and quality for pregnant individuals with OUD. It is intended to serve as a roadmap for our own study and for future related work within the context of substance use disorders and pregnancy.
Impaired anaplerosis is a major contributor to glycolysis inhibitor toxicity in glioma
Authors: Khadka Sunada , Arthur Kenisha , Barekatain Yasaman , Behr Eliot , Washington Mykia , Ackroyd Jeffrey , Crowley Kaitlyn , Suriyamongkol Pornpa , Lin Yu-Hsi , Pham Cong-Dat , Zielinski Rafal , Trujillo Marissa , Galligan James , Georgiou Dimitra K. , Asara John , Muller Florian 
Published: June 2021

Abstract
Background
Reprogramming of metabolic pathways is crucial to satisfy the bioenergetic and biosynthetic demands and maintain the redox status of rapidly proliferating cancer cells. In tumors, the tricarboxylic acid (TCA) cycle generates biosynthetic intermediates and must be replenished (anaplerosis), mainly from pyruvate and glutamine. We recently described a novel enolase inhibitor, HEX, and its pro-drug POMHEX. Since glycolysis inhibition would deprive the cell of a key source of pyruvate, we hypothesized that enolase inhibitors might inhibit anaplerosis and synergize with other inhibitors of anaplerosis, such as the glutaminase inhibitor, CB-839.

Methods
We analyzed polar metabolites in sensitive (ENO1-deleted) and resistant (ENO1-WT) glioma cells treated with enolase and glutaminase inhibitors. We investigated whether sensitivity to enolase inhibitors could be attenuated by exogenous anaplerotic metabolites. We also determined the synergy between enolase inhibitors and the glutaminase inhibitor CB-839 in glioma cells in vitro and in vivo in both intracranial and subcutaneous tumor models.

Results
Metabolomic profiling of ENO1-deleted glioma cells treated with the enolase inhibitor revealed a profound decrease in the TCA cycle metabolites with the toxicity reversible upon exogenous supplementation of supraphysiological levels of anaplerotic substrates, including pyruvate. ENO1-deleted cells also exhibited selective sensitivity to the glutaminase inhibitor CB-839, in a manner rescuable by supplementation of anaplerotic substrates or plasma-like media PlasmaxTM. In vitro, the interaction of these two drugs yielded a strong synergistic interaction but the antineoplastic effects of CB-839 as a single agent in ENO1-deleted xenograft tumors in vivo were modest in both intracranial orthotopic tumors, where the limited efficacy could be attributed to the blood-brain barrier (BBB), and subcutaneous xenografts, where BBB penetration is not an issue. This contrasts with the enolase inhibitor HEX, which, despite its negative charge, achieved antineoplastic effects in both intracranial and subcutaneous tumors.

Conclusion
Together, these data suggest that at least for ENO1-deleted gliomas, tumors in vivo—unlike cells in culture—show limited dependence on glutaminolysis and instead primarily depend on glycolysis for anaplerosis. Our findings reinforce the previously reported metabolic idiosyncrasies of in vitro culture and suggest that cell culture media nutrient composition more faithful to the in vivo environment will more accurately predict in vivo efficacy of metabolism targeting drugs.
‘Pediatric Bipolar Disorder’ rates are still lower than claimed: a re-examination of eight epidemiological surveys used by an updated meta-analysis
Authors: Parry Peter , Allison Stephen , Bastiampillai Tarun 
Published: June 2021

Abstract
Background
‘Pediatric bipolar disorder’ (PBD) is a controversial diagnosis with varying rates of clinical diagnosis. A highly cited meta-analysis (Van Meter et al. 2011) of a dozen epidemiological surveys suggested a global community prevalence of PBD of 1.8%. This was updated to 3.9% with eight additional surveys (Van Meter et al. 2019a). In terms of the Cochrane Handbook for Systematic Reviews of Interventions, the heterogenous community surveys were arguably unsuitable for statistical meta-analysis and warranted a narrative analysis. A narrative analysis (Parry et al. 2018) of the original 12 surveys concluded rates of PBD were substantially lower than 1.8% and led to a nine-article debate on the validity, arguable overdiagnosis and iatrogenic aspects of the PBD diagnosis (e.g. Carlson and Dubicka Child Adolesc Mental Health 21:86–87, 2019). This article extends the narrative analysis to include the eight newer community surveys.

Methods
A narrative analysis of the methodologies and the prevalence rates reported by the epidemiological surveys.

Results
Across all twenty surveys there was significant variation in methodologies and reported prevalence rates. Of the eight newer surveys, five (two Brazilian, one English, one Turkish, one United States) provided information of pre-adolescent prevalence rates of bipolar spectrum disorder. These pre-adolescent rates were zero or close to zero. Rates of adolescent hypomania and mania were higher, but follow-up data in two studies suggested hypomania might sometimes achieve prolonged remission or not lead to adult bipolar disorder.

Limitations
Methods in the original surveys vary and criteria used for various bipolar diagnoses were not always fully described. This limitation applies to a narrative analysis but also to a statistical meta-analysis.

Conclusion
Bipolar disorder is very rare in childhood and rare in adolescence. PBD as a diagnostic construct fails to correlate with adult bipolar disorder and the term should be abandoned. Hypomanic syndromes in adolescence may not always progress to adult bipolar disorder. Early diagnosis of bipolar disorder is important, but over-diagnosis risks adverse iatrogenic consequences.
Can use of pictograms reduce liquid medication administration errors by mothers? An interventional study
Authors: Patidar Pawan , Mathur Aditya , Pathak Ashish 
Published: June 2021

Abstract
Background
Liquid medication dosing errors (LMDE) made by caregivers affect treatment in children, but this is not a well-studied topic in many low-and middle-income countries including in India.

Methods
An intervention study was conducted among mothers attending a pediatric outpatient clinic of a tertiary care setting in Ujjain, India. The mothers randomly measured 12 volumes of a paracetamol liquid preparation by using a dropper (0.5 and 1 mL), measuring cup (2.5 and 5 mL), and calibrated spoon (2.5 and 5 mL) each with two instructions—oral-only measurement session (OMS) and oral plus pictogram measurement session (OPMS, the intervention). The main outcome was dosing error prevalence. The effectiveness of the intervention was assessed by measuring effect size. Risk factors for maximum LMDE were explored using backward multivariate logistic regression models. A P value of < 0.05 was considered statistically significant.

Results
In total, 310 mothers [mean (± SD) age, 30.2 (± 4.18) years] were included. LMDE prevalence in the OMS versus OPMS for dropper 0.5 mL was 60% versus 48%; for l mL dropper was 63% versus 54%; for 2.5 mL cup 62% versus 54%; for 2.5 calibrated spoon 66% versus 59%; 5 mL cup 69% versus 57%; and 5 mL calibrated spoon 68% versus 55%. Comparing OMS with OPMS, underdosing was minimum with the calibrated spoon for 2.5 mL (OR 4.39) and maximum with the dropper for 1 mL (OR 9.40), and overdosing was minimum with the dropper for 0.5 mL (OR 7.12) and maximum with the calibrated spoon for 2.5 mL (OR 13.24). The effect size (dCohen) of the intervention OPMS was 1.86–6.4. Risk factors for the most prevalent dosing error, that is, with the calibrated spoon for 2.5 mL, were increasing age of the mother (aOR 1.08; P = 0.026) and nuclear family (aOR 2.83; P = 0.002). The risk of dosing errors decreased with higher education of the mothers.

Conclusions
Pictograms can effectively minimize LMDE even in less educated mothers.