bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human plasma plasminogen internalization route in Plasmodium falciparum-infected erythrocytes
Authors: El Chamy Maluf Sarah , Icimoto Marcelo Yudi , Melo Pollyana Maria Saud , Budu Alexandre , Coimbra Rita , Gazarini Marcos Leoni , Carmona Adriana Karaoglanovic 
Published: August 2020

Abstract
Background
The intra-erythrocytic development of the malaria parasite Plasmodium falciparum depends on the uptake of a number of essential nutrients from the host cell and blood plasma. It is widely recognized that the parasite imports low molecular weight solutes from the plasma and the consumption of these nutrients by P. falciparum has been extensively analysed. However, although it was already shown that the parasite also imports functional proteins from the vertebrate host, the internalization route through the different infected erythrocyte membranes has not yet been elucidated. In order to further understand the uptake mechanism, the study examined the trafficking of human plasminogen from the extracellular medium into P. falciparum-infected red blood cells.

Methods
Plasmodium falciparum clone 3D7 was cultured in standard HEPES-buffered RPMI 1640 medium supplemented with 0.5% AlbuMAX. Exogenous human plasminogen was added to the P. falciparum culture and the uptake of this protein by the parasites was analysed by electron microscopy and Western blotting. Immunoprecipitation and mass spectrometry were performed to investigate possible protein interactions that may assist plasminogen import into infected erythrocytes. The effect of pharmacological inhibitors of different cellular physiological processes in plasminogen uptake was also tested.

Results
It was observed that plasminogen was selectively internalized by P. falciparum-infected erythrocytes, with localization in plasma membrane erythrocyte and parasite’s cytosol. The protein was not detected in parasitic food vacuole and haemoglobin-containing vesicles. Furthermore, in erythrocyte cytoplasm, plasminogen was associated with the parasite-derived membranous structures tubovesicular network (TVN) and Maurer’s clefts. Several proteins were identified in immunoprecipitation assay and may be involved in the delivery of plasminogen across the P. falciparum multiple compartments.

Conclusion
The findings here reported reveal new features regarding the acquisition of plasma proteins of the host by P. falciparum-infected erythrocytes, a mechanism that involves the exomembrane system, which is distinct from the haemoglobin uptake, clarifying a route that may be potentially targeted for inhibition studies.
Therapeutic monoclonal antibody targeting of neuronal pentraxin receptor to control metastasis in gastric cancer
Authors: Kanda Mitsuro , Shimizu Dai , Sawaki Koichi , Nakamura Shunsuke , Umeda Shinichi , Miwa Takashi , Tanaka Haruyoshi , Tanaka Chie , Hayashi Masamichi , Iguchi Yohei , Yamada Suguru , Katsuno Masahisa , Kodera Yasuhiro 
Published: August 2020

Abstract
Background
Controlling metastasis is essential for improving the prognosis of patients with gastric cancer (GC). Here, we aimed to identify a molecule required for GC metastasis and to investigate its potential utility as a target for the development of therapeutic antibodies (Abs).

Methods
Transcriptome and bioinformatics analyses of human GC cell lines identified the neuronal pentraxin receptor (NPTXR) as a candidate molecule. NPTXR function was probed by modulating its expression in GC cells and assessing the effects on intracellular signaling and malignant behaviors in vitro and in mouse xenograft models. We also generated anti-NPTXR Abs and Nptxr−/− mice, and assessed the clinical significance of NPTXR expression in GC specimens.

Results
NPTXR mRNA expression in clinical specimens was associated with disease progression and was significantly higher in tissues from GC patients with distant metastasis compared with those without. NPTXR regulated expression of genes involved in metastatic behaviors as well as activation of the PI3K–AKT–mTOR, FAK–JNK, and YAP signaling pathways. NPTXR silencing promoted caspase-mediated apoptosis and attenuated GC cell proliferation, cell cycle progression, migration, invasion, adhesion, stem cell-like properties, and resistance to 5-fluorouracil in vitro, and also inhibited the tumorigenicity of GC cells in vivo. Anti-NPTXR Abs inhibited GC peritoneal metastasis in mice. Nptxr−/− mice showed no abnormalities in reproduction, development, metabolism, or motor function.

Conclusions
NPTXR plays an essential role in controlling the malignant behavior of GC cells in vitro and in vivo. NPTXR-targeting Abs may thus have utility as novel diagnostic tools and/or treatment modalities for GC.
The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19
Authors: Xu Yi , Baylink David J. , Chen Chien-Shing , Reeves Mark E. , Xiao Jeffrey , Lacy Curtis , Lau Eric , Cao Huynh 
Published: August 2020

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has led to a declaration of a Public Health Emergency of International Concern by the World Health Organization. As of May 18, 2020, there have been more than 4.7 million cases and over 316,000 deaths worldwide. COVID-19 is caused by a highly infectious novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to an acute infectious disease with mild-to-severe clinical symptoms such as flu-like symptoms, fever, headache, dry cough, muscle pain, loss of smell and taste, increased shortness of breath, bilateral viral pneumonia, conjunctivitis, acute respiratory distress syndromes, respiratory failure, cytokine release syndrome (CRS), sepsis, etc. While physicians and scientists have yet to discover a treatment, it is imperative that we urgently address 2 questions: how to prevent infection in immunologically naive individuals and how to treat severe symptoms such as CRS, acute respiratory failure, and the loss of somatosensation. Previous studies from the 1918 influenza pandemic have suggested vitamin D’s non-classical role in reducing lethal pneumonia and case fatality rates. Recent clinical trials also reported that vitamin D supplementation can reduce incidence of acute respiratory infection and the severity of respiratory tract diseases in adults and children. According to our literature search, there are no similar findings of clinical trials that have been published as of July 1st, 2020, in relation to the supplementation of vitamin D in the potential prevention and treatment for COVID-19. In this review, we summarize the potential role of vitamin D extra-renal metabolism in the prevention and treatment of the SARS-CoV-2 infection, helping to bring us slightly closer to fulfilling that goal. We will focus on 3 major topics here:

Vitamin D might aid in preventing SARS-CoV-2 infection:

Vitamin D: Overview of Renal and Extra-renal metabolism and regulation.

Vitamin D: Overview of molecular mechanism and multifaceted functions beyond skeletal homeostasis.

Vitamin D: Overview of local immunomodulation in human infectious diseases.

Anti-viral infection.

Anti-malaria and anti-systemic lupus erythematosus (SLE).

Vitamin D might act as a strong immunosuppressant inhibiting cytokine release syndrome in COVID-19:

Vitamin D: Suppression of key pro-inflammatory pathways including nuclear factor kappa B (NF-kB), interleukin-6 (IL-6), and tumor necrosis factor (TNF).

Vitamin D might prevent loss of neural sensation in COVID-19 by stimulating expression of neurotrophins like Nerve Growth Factor (NGF):

Vitamin D: Induction of key neurotrophic factors.

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Rectus femoris hyperreflexia contributes to Stiff-Knee gait after stroke
Authors: Akbas Tunc , Kim Kyoungsoon , Doyle Kathleen , Manella Kathleen , Lee Robert , Spicer Patrick , Knikou Maria , Sulzer James 
Published: August 2020

Abstract
Background
Stiff-Knee gait (SKG) after stroke is often accompanied by decreased knee flexion angle during the swing phase. The decreased knee flexion has been hypothesized to originate from excessive quadriceps activation. However, it is unclear whether hyperreflexia plays a role in this activation. The goal of this study was to establish the relationship between quadriceps hyperreflexia and knee flexion angle during walking in post-stroke SKG.

Methods
The rectus femoris (RF) H-reflex was recorded in 10 participants with post-stroke SKG and 10 healthy controls during standing and walking at the pre-swing phase. In order to attribute the pathological neuromodulation to quadriceps muscle hyperreflexia and activation, healthy individuals voluntarily increased quadriceps activity using electromyographic (EMG) feedback during standing and pre-swing upon RF H-reflex elicitation.

Results
We observed a negative correlation (R = − 0.92, p = 0.001) between knee flexion angle and RF H-reflex amplitude in post-stroke SKG. In contrast, H-reflex amplitude in healthy individuals in presence (R = 0.47, p = 0.23) or absence (R = − 0.17, p = 0.46) of increased RF muscle activity was not correlated with knee flexion angle. We observed a body position-dependent RF H-reflex modulation between standing and walking in healthy individuals with voluntarily increased RF activity (d = 2.86, p = 0.007), but such modulation was absent post-stroke (d = 0.73, p = 0.296).

Conclusions
RF reflex modulation is impaired in post-stroke SKG. The strong correlation between RF hyperreflexia and knee flexion angle indicates a possible regulatory role of spinal reflex excitability in post-stroke SKG. Interventions targeting quadriceps hyperreflexia could help elucidate the causal role of hyperreflexia on knee joint function in post-stroke SKG.
3D characterization of walnut morphological traits using X-ray computed tomography
Authors: Bernard Anthony , Hamdy Sherif , Le Corre Laurence , Dirlewanger Elisabeth , Lheureux Fabrice 
Published: August 2020

AbstractBackgroundWalnuts are grown worldwide in temperate areas and producers are facing an increasing demand. In a climate change context, the industry also needs cultivars that provide fruits of quality. This quality includes satisfactory filling ratio, thicker shell, ease of cracking, smooth shell and round-shaped walnut, and larger nut size. These desirable traits have been analysed so far using calipers or micrometers, but it takes a lot of time and requires the destruction of the sample. A challenge to take up is to develop an accurate, fast and non-destructive method for quality-related and morphometric trait measurements of walnuts, that are used to characterize new cultivars or collections in any germplasm management process.ResultsIn this study, we develop a method to measure different morphological traits on several walnuts simultaneously such as morphometric traits (nut length, nut face and profile diameters), traits that previously required opening the nut (shell thickness, kernel volume and filling kernel/nut ratio) and traits that previously were difficult to quantify (shell rugosity, nut sphericity, nut surface area and nut shape). These measurements were obtained from reconstructed 3D images acquired by X-ray computed tomography (CT). A workflow was created including several steps: noise elimination, walnut individualization, properties extraction and quantification of the different parts of the fruit. This method was applied to characterize 50 walnuts of a part of the INRAE walnut germplasm collection made of 161 unique accessions, obtained from the 2018 harvest. Our results indicate that 50 walnuts are sufficient to phenotype the fruit quality of one accession using X-ray CT and to find correlations between the morphometric traits. Our imaging workflow is suitable for any walnut size or shape and provides new and more accurate measurements.ConclusionsThe fast and accurate measurement of quantitative traits is of utmost importance to conduct quantitative genetic analyses or cultivar characterization. Our imaging workflow is well adapted for accurate phenotypic characterization of a various range of traits and could be easily applied to other important nut crops.
Does arthroscopic repair show superiority over open repair of lateral ankle ligament for chronic lateral ankle instability: a systematic review and meta-analysis
Authors: Zhi Xiaosong , Lv Zhuman , Zhang Chen , Kong Changwang , Wei Shijun , Xu Feng 
Published: August 2020

AbstractBackgroundThere is still no definite consensus on whether arthroscopic repair shows superiority over open repair for chronic lateral ankle instability. We conducted a systematic review and meta-analysis of the current comparative studies to make a generalized analysis.MethodsPubMed, Embase, and Web of Science databases were searched from inception to April 2020. Included studies were assessed by the level of evidence and quality of evidence (Cochrane Handbook or MINORS). The process of data extraction was conducted by two independent authors. The comparative results of clinical outcomes, stress radiographic outcomes, and complication rates between two groups were pooled. Statistical analysis was performed using STATA.ResultsNine comparative studies for a total of 473 patients (250 arthroscopic repair, 223 open repair) were included. For the clinical outcomes, a significant difference was found in favor of arthroscopic repair with regard to AOFAS scores (MD 0.32, 95% CI 0.12 to 0.53,I2= 7.7%,P= .370) and VAS scores (MD − 0.30, 95% CI − 0.54 to − 0.05,I2= 48.3%,P= .102). No significant difference was found regarding to stress radiographic outcomes. Importantly, the total complication rate (RR 0.88, 95% CI 0.51 to 1.49,I2= 0%,P= .957) as well as nerve complication rate (RR 1.21, 95% CI 0.53 to 2.75,I2= 0%,P= .975) of arthroscopic repair group is not significantly different to that of open repair group.ConclusionsArthroscopic repair for lateral ankle instability shows excellent clinical results comparable to open repair. Especially, arthroscopic repair might alleviate more pain due to the minimally invasive procedure. Patients receiving arthroscopic repair do not result in a higher total complication rate and nerve injury rate.
What we already know about rhubarb: a comprehensive review
Authors: Xiang Hong , Zuo Jiaxin , Guo Fangyue , Dong Deshi 
Published: August 2020

AbstractRhubarb (also named Rhei or Dahuang), one of the most ancient and important herbs in traditional Chinese medicine (TCM), belongs to theRheum L.genus from the Polygonaceae family, and its application can be traced back to 270 BC in “Shen Nong Ben Cao Jing”. Rhubarb has long been used as an antibacterial, anti-inflammatory, anti-fibrotic and anticancer medicine in China. However, for a variety of reasons, such as origin, variety and processing methods, there are differences in the effective components of rhubarb, which eventually lead to decreased quality and poor efficacy. Additionally, although some papers have reviewed the relationship between the active ingredients of rhubarb and pharmacologic actions, most studies have concentrated on one or several aspects, although there has been great progress in rhubarb research in recent years. Therefore, this review aims to summarize recent studies on the geographic distribution, taxonomic identification, pharmacology, clinical applications and safety issues related to rhubarb and provide insights into the further development and application of rhubarb in the future.
PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection
Authors: Tang Zheng-Zheng , Sliwoski Gregory R. , Chen Guanhua , Jin Bowen , Bush William S. , Li Bingshan , Capra John A. 
Published: August 2020

AbstractGermline disease-causing variants are generally more spatially clustered in protein 3-dimensional structures than benign variants. Motivated by this tendency, we develop a fast and powerful protein-structure-based scan (PSCAN) approach for evaluating gene-level associations with complex disease and detecting signal variants. We validate PSCAN’s performance on synthetic data and two real data sets for lipid traits and Alzheimer’s disease. Our results demonstrate that PSCAN performs competitively with existing gene-level tests while increasing power and identifying more specific signal variant sets. Furthermore, PSCAN enables generation of hypotheses about the molecular basis for the associations in the context of protein structures and functional domains.
Differential contribution of Anopheles coustani and Anopheles arabiensis to the transmission of Plasmodium falciparum and Plasmodium vivax in two neighbouring villages of Madagascar
Authors: Goupeyou-Youmsi Jessy , Rakotondranaivo Tsiriniaina , Puchot Nicolas , Peterson Ingrid , Girod Romain , Vigan-Womas Inès , Paul Richard , Ndiath Mamadou Ousmane , Bourgouin Catherine 
Published: August 2020

AbstractBackgroundMalaria is still a heavy public health concern in Madagascar. Few studies combining parasitology and entomology have been conducted despite the need for accurate information to design effective vector control measures. In a Malagasy region of moderate to intense transmission of bothPlasmodium falciparumandP. vivax, parasitology and entomology have been combined to survey malaria transmission in two nearby villages.MethodsCommunity-based surveys were conducted in the villages of Ambohitromby and Miarinarivo at three time points (T1, T2 and T3) during a single malaria transmission season. Human malaria prevalence was determined by rapid diagnostic tests (RDTs), microscopy and real-time PCR. Mosquitoes were collected by human landing catches and pyrethrum spray catches and the presence ofPlasmodiumsporozoites was assessed by TaqMan assay.ResultsMalaria prevalence was not significantly different between villages, with an average of 8.0% by RDT, 4.8% by microscopy and 11.9% by PCR. This was mainly due toP. falciparumand to a lesser extent toP. vivax. However, there was a significantly higher prevalence rate as determined by PCR at T2 ($$\chi_{2}^{2}$$χ22= 7.46,P= 0.025). Likewise, mosquitoes were significantly more abundant at T2 ($$\chi_{2}^{2}$$χ22= 64.8,P< 0.001), especially in Ambohitromby. At T1 and T3 mosquito abundance was higher in Miarinarivo than in Ambohitromby ($$\chi_{2}^{2}$$χ22= 14.92,P< 0.001). Of 1550Anophelesmosquitoes tested, 28 (1.8%) were found carryingPlasmodiumsporozoites. The entomological inoculation rate revealed thatAnopheles coustaniplayed a major contribution in malaria transmission in Miarinarivo, being responsible of 61.2 infective bites per human (ib/h) during the whole six months of the survey, whereas, it wasAn. arabiensis, with 36 ib/h, that played that role in Ambohitromby.ConclusionsDespite a similar malaria prevalence in two nearby villages, the entomological survey showed a different contribution ofAn. coustaniandAn. arabiensisto malaria transmission in each village. Importantly, the suspected secondary malaria vectorAn. coustani, was found playing the major role in malaria transmission in one village. This highlights the importance of combining parasitology and entomology surveys for better targeting local malaria vectors. Such study should contribute to the malaria pre-elimination goal established under the 2018–2022 National Malaria Strategic Plan.
Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis
Authors: Siafis Spyridon , Çıray Oğulcan , Schneider-Thoma Johannes , Bighelli Irene , Krause Marc , Rodolico Alessandro , Ceraso Anna , Deste Giacomo , Huhn Maximilian , Fraguas David , Mavridis Dimitris , Charman Tony , Murphy Declan G. , Parellada Mara , Arango Celso , Leucht Stefan 
Published: August 2020

Abstract
Background
Placebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms.

Methods
We searched ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019) for randomized pharmacological and dietary supplement placebo-controlled trials (RCTs) with a minimum of seven days of treatment. Single-group meta-analyses were conducted using a random-effects model. Standardized mean changes (SMC) of core symptoms in placebo arms were the primary outcomes and placebo positive response rates were a secondary outcome. Predictors of placebo response were investigated with meta-regression analyses. The protocol was registered with PROSPERO ID CRD42019125317.

Results
Eighty-six RCTs with 2360 participants on placebo were included in our analysis (87% in children/adolescents). The majority of trials were small, single-center with a duration of 8–12 weeks and published after 2009. Placebo response in social-communication difficulties was SMC = − 0.32, 95% CI [− 0.39, − 0.25], in repetitive behaviors − 0.23[− 0.32, − 0.15] and in scales measuring overall core symptoms − 0.36 [− 0.46, − 0.26]. Overall, 19%, 95% CI [16–22%] of participants were at least much improved with placebo. Caregiver (vs. clinician) ratings, lower risk of bias, flexible-dosing, larger sample sizes and number of sites, less recent publication year, baseline levels of irritability, and the use of a threshold of core symptoms at inclusion were associated with larger placebo response in at least a core symptom domain.

Limitations
About 40% of the trials had an apparent focus on core symptoms. Investigation of the differential impact of predictors on placebo and drug response was impeded by the use of diverse experimental interventions with essentially different mechanisms of action. An individual-participant-data meta-analysis could allow for a more fine-grained analysis and provide more informative answers.

Conclusions
Placebo response in ASD was substantial and predicted by design- and participant-related factors, which could inform the design of future trials in order to improve the detection of efficacy in core symptoms. Potential solutions could be the minimization and careful selection of study sites as well as rigorous participant enrollment and the use of measurements of change not solely dependent on caregivers.
The needle and the damage done: musculoskeletal and vascular complications associated with injected drug use
Authors: Delaney Francis T. , Stanley Emma , Bolster Ferdia 
Published: August 2020

AbstractInjected drug use is associated with a wide range of medical complications which are predominantly musculoskeletal and vascular in nature. Illicit drug use is increasing worldwide. Patients with complications of injected drug use often present in a non-specific manner without a reliable clinical history. Musculoskeletal complications are typically infective in aetiology and may vary widely in severity from mild to life-threatening. A multimodal imaging approach is often required for both diagnostic imaging and image-guided sampling. Plain radiographs are often an important initial test, for example in identifying retained needles from injection. Ultrasound and CT play important roles in the assessment of complex soft tissue complications and MRI is the imaging modality of choice for bone and joint disorders. Vascular complications may be venous or arterial in nature and usually occur locally at the injection site. These complications may be related to direct injury to the vessel wall by a needle, or secondary to local infection and inflammation. A multimodal imaging strategy is also often required in the assessment of these vascular complications, typically involving a combination of ultrasound and CT. Familiarity with the multimodal imaging features of the complications related to injected drug use is crucially important as they may be rapidly progressive and life-threatening and require timely diagnosis.