bluuebunny/crossref_metadata_2025 huggingface dataset:
Equine grass sickness in italy: a case series study
Authors: Laus Fulvio , Corsalini Jacopo , Mandara Maria Teresa , Bazzano Marilena , Bertoletti Alice , Gialletti Rodolfo
Published: August 2021

Background

Equine grass sickness (EGS) has been reported in several European and extra-European countries. Despite this, no scientific paper about clinical cases of EGS in Italy has been published. EGS is a disease affecting almost exclusively horses kept on pasture, characterized by clinical signs related to lesions in autonomic nervous system (ANS), particularly in the enteric nervous system (ENS). According to clinical presentation, acute, subacute and chornic syndromes can be observed, with various sympthoms including dullness, anorexia, dysphagia, drooling of saliva, tachycardia, ptosis, patchy sweating and muscle fasciculations. In horses affected by acute forms, mild to moderate abdominal pain and large volumes of nasogastric reflux can be observed. The etiology is still speculative and many hypothesis have been proposed to explain the pathogenesis.

Case presentation

The present study describes four cases of EGS (one subacute and three chronic forms) occurred in Central Italy during early spring. In all the cases included in the study, the prognosis was poor and the horses were euthanized. The diagnosis was confirmed by histological examination of ANS or ENS. In two cases, in vivo diagnosis was obtained by histological examination of enteric bioptic samples collected during laparoscopy.

Conclusions

EGS in Italy could be underdiagnosed and incidence understimated. Greater awareness should be applied in Italy for the inclusion of EGS in differential diagnosis for horses presenting clinical signs of abdominal pain associated or not with gastric reflux and muscular fasciculation. All the cases in this study concerned horses kept in the same pasture, confirming a possible premise-linked and management-linked factors on the ethiopathogenesis of EGS. The age of horses ranged from 2 to 6 years, that is consistent with the risk factor age for EGS (from 2 to 7 years of age). Previous suspected EGS diagnosis in the same livestock and recent cool dry weather were considered additional potential risk factors.
Effect of prone positioning on oxygenation and static respiratory system compliance in COVID-19 ARDS vs. non-COVID ARDS
Authors: Park Jimyung , Lee Hong Yeul , Lee Jinwoo , Lee Sang-Min
Published: August 2021

Background

Prone positioning is recommended for patients with moderate-to-severe acute respiratory distress syndrome (ARDS) receiving mechanical ventilation. While the debate continues as to whether COVID-19 ARDS is clinically different from non-COVID ARDS, there is little data on whether the physiological effects of prone positioning differ between the two conditions. We aimed to compare the physiological effect of prone positioning between patients with COVID-19 ARDS and those with non-COVID ARDS.

Methods

We retrospectively compared 23 patients with COVID-19 ARDS and 145 patients with non-COVID ARDS treated using prone positioning while on mechanical ventilation. Changes in PaO2/FiO2 ratio and static respiratory system compliance (Crs) after the first session of prone positioning were compared between the two groups: first, using all patients with non-COVID ARDS, and second, using subgroups of patients with non-COVID ARDS matched 1:1 with patients with COVID-19 ARDS for baseline PaO2/FiO2 ratio and static Crs. We also evaluated whether the response to the first prone positioning session was associated with the clinical outcome.

Results

When compared with the entire group of patients with non-COVID ARDS, patients with COVID-19 ARDS showed more pronounced improvement in PaO2/FiO2 ratio [adjusted difference 39.3 (95% CI 5.2–73.5) mmHg] and static Crs [adjusted difference 3.4 (95% CI 1.1–5.6) mL/cmH2O]. However, these between-group differences were not significant when the matched samples (either PaO2/FiO2-matched or compliance-matched) were analyzed. Patients who successfully discontinued mechanical ventilation showed more remarkable improvement in PaO2/FiO2 ratio [median 112 (IQR 85–144) vs. 35 (IQR 6–52) mmHg, P = 0.003] and static compliance [median 5.7 (IQR 3.3–7.7) vs. − 1.0 (IQR − 3.7–3.0) mL/cmH2O, P = 0.006] after prone positioning compared with patients who did not. The association between oxygenation and Crs responses to prone positioning and clinical outcome was also evident in the adjusted competing risk regression.

Conclusions

In patients with COVID-19 ARDS, prone positioning was as effective in improving respiratory physiology as in patients with non-COVID ARDS. Thus, it should be actively considered as a therapeutic option. The physiological response to the first session of prone positioning was predictive of the clinical outcome of patients with COVID-19 ARDS.
Feasibility and outcomes of bronchial artery embolization in patients with non-massive hemoptysis
Authors: Hwang Jung Han , Kim Jeong Ho , Park Suyoung , Lee Ki Hyun , Park So Hyun
Published: August 2021

Purpose

To evaluate the safety, efficacy, and long-term outcome of bronchial artery embolization (BAE) in the treatment of non-massive hemoptysis and the prognostic factors associated with recurrent bleeding.

Materials and methods

From March 2005 to September 2014, BAE was performed in 233 patients with non-massive hemoptysis. All patients had a history of persistent or recurrent hemoptysis despite conservative medical treatment. We assessed the technical and clinical success, recurrence, prognostic factors related to recurrent bleeding, recurrence-free survival rate, additional treatment, and major complications in all the patients.

Results

Technical success was achieved in 224 patients (96.1%), and clinical success was obtained in 219 (94.0%) of the 233 patients. In addition, 64 patients (27.5%) presented hemoptysis recurrence with median time of 197 days after embolization. Tuberculosis sequelae and presence of aberrant bronchial artery or non-bronchial systemic collaterals were significantly related to recurrent bleeding (p < 0.05). The use of Histoacryl-based embolic materials significantly reduced the recurrent bleeding rate (p < 0.05). Patient who had a tuberculosis sequelae showed a significantly lower recurrence-free survival rate (p = 0.013). Presence of aberrant bronchial artery or non-bronchial systemic collaterals showed a statistically significant correlation with recurrence-free survival rate (p = 0.021). No patients had major complications during follow-up.

Conclusions

BAE is a safe and effective treatment to manage non-massive hemoptysis. The procedure may offer a better long-term control of recurrent hemoptysis and quality of life than conservative therapy alone.
NAT10 as a potential prognostic biomarker and therapeutic target for HNSCC
Authors: Tao Wenjie , Tian Guocai , Xu Shengming , Li Jiayi , Zhang Zhiyuan , Li Jiang
Published: August 2021

Background

Increasing evidence has demonstrated the critical roles of mRNA modification regulators on multiple types of cancers. However, it is still poorly known about the prognostic and therapeutic value of mRNA modification regulators in HNSCC.

Methods

The gene expression profile of 36 mRNA modification regulators and their corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Stepwise regression in R with both directions was used to construct a model for the prognosis of HNSCC. Univariate Cox regression survival analysis was performed to identify the most significant risk gene. Gene set enrichment analysis (GSEA) was applied to determine the cancer-associated pathways with NAT10. Immunohistochemistry (IHC) staining was performed to evaluate the expression of NAT10 in formalin fixed paraffin-embedded (FFPE) samples of HNSCC. Univariate and multivariate Cox regression survival analysis performed to identify the independent risk factors associated with the OS of patients with HNSCC. HNSCC cell lines (Cal-27, FaDu, and Detroit-562) were transfected with short interfering RNA (siRNA) targeting NAT10 or treated with Remodelin, a small-molecule inhibitor of NAT10. Knockdown efficiency of siRNA was assessed by quantitative real-time PCR (qRT-PCR) and western blotting. In addition, CCK-8 assay, scratch assay and transwell assay were used to examine the proliferation, migration, and invasion abilities of the three HNSCC cell lines after NAT10 was inhibited genetically and pharmaceutically. Cell cycle and cell apoptosis assays were performed by flow cytometry. Finally, the therapeutic value of Remodelin in HNSCC was evaluated via a patient-derived xenograft (PDX) model. The statistical analysis was performed with SPSS 23.0.

Results

A risk prediction model containing 10 mRNA modification regulators was constructed and showed prognostic value in HNSCC. NAT10 was further identified as a key risk gene and independent prognostic factor in TCGA HNSCC dataset. The GSEA analysis suggested that high NAT10 expression was associated with MYC, E2F, G2M checkpoint, mTORC1, DNA repair and oxidative phosphorylation pathways. NAT10 protein expression was significantly up-regulated in tumour cells compared to normal epithelial cells in FFPE samples and increased NAT10 protein expression was correlated with poor overall survival of 267 HNSCC patients. Genetic depletion of NAT10 using siRNA or chemical inhibition of NAT10 using Remodelin resulted in reduced cell proliferation, migration and invasion abilities in Cal-27, FaDu and Detroit-562 cells. Knockdown of NAT10 using siRNA significantly increased cell cycle arrest in S/G2-phase. Remodelin significantly inhibited tumour growth and tumour cell proliferation in the PDX model of HNSCC.

Conclusions

NAT10 could be a potential prognostic marker and a therapeutic target for HNSCC.
The effects of fat consumption on low-density lipoprotein particle size in healthy individuals: a narrative review
Authors: Froyen Erik
Published: August 2021

Cardiovascular disease (CVD) is the number one contributor to death in the United States and worldwide. A risk factor for CVD is high serum low-density lipoprotein cholesterol (LDL-C) concentrations; however, LDL particles exist in a variety of sizes that may differentially affect the progression of CVD. The small, dense LDL particles, compared to the large, buoyant LDL subclass, are considered to be more atherogenic. It has been suggested that replacing saturated fatty acids with monounsaturated and polyunsaturated fatty acids decreases the risk for CVD. However, certain studies are not in agreement with this recommendation, as saturated fatty acid intake did not increase the risk for CVD, cardiovascular events, and/or mortality. Furthermore, consumption of saturated fat has been demonstrated to increase large, buoyant LDL particles, which may explain, in part, for the differing outcomes regarding fat consumption on CVD risk. Therefore, the objective was to review intervention trials that explored the effects of fat consumption on LDL particle size in healthy individuals. PubMed and Web of Science were utilized during the search process for journal articles. The results of this review provided evidence that fat consumption increases large, buoyant LDL and/or decreases small, dense LDL particles, and therefore, influences CVD risk.
Cyanidin-3-glucoside suppresses the progression of lung adenocarcinoma by downregulating TP53I3 and inhibiting PI3K/AKT/mTOR pathway
Authors: Chen Xiaojun , Zhang Weixia , Xu Xiuzhen
Published: August 2021

Background

The aim of this study is to unravel the role of Cyanidin-3-glucoside (C3G) and its potential mechanisms in lung adenocarcinoma (LUAD).

Methods

The cell clones, proliferation, apoptosis, migration, and invasion in H1299 and A549 cells were determined by colony formation assay, 5-ethynyl-20 deoxyuridine (EdU) assay, flow cytometry, and transwell assay, respectively. The expression of p53-induced gene 3 (TP53I3) was assessed and the prognostic values of TP53I3 in LUAD via the dataset from the Cancer Genome Atlas (TCGA). In addition, the mRNA and protein expressions were detected by quantitative real-time PCR (qRT-PCR) and western blot.

Results

C3G inhibited the proliferation, migration, and invasion of, and also promoted the apoptosis in H1299 and A549 cells. The database of TCGA showed TP53I3 was highly expressed in LUAD tissues and correlated with the poor prognosis of LUAD patients. Moreover, we also found that C3G inhibited the proliferation, migration and invasion, and promoted apoptosis in H1299 and A549 cells by downregulating TP53I3. Additionally, C3G could inhibit the activation of phosphatidylinositol 3′-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in H1299 and A549 cells by downregulating TP53I3.

Conclusion

This study demonstrated that C3G could inhibit the proliferation, migration and invasion, and also facilitate the apoptosis through downregulating TP53I3 and inhibiting PI3K/AKT/mTOR pathway in LUAD.
Inhibition of autophagy by CRMP2-derived peptide ST2-104 (R9-CBD3) via a CaMKKβ/AMPK/mTOR pathway contributes to ischemic postconditioning-induced neuroprotection against cerebral ischemia-reperfusion injury
Authors: Yao Yuan , Ji Yingshi , Ren Jinghong , Liu Huanyu , Khanna Rajesh , Sun Li
Published: August 2021

Cerebral ischemia, a common cerebrovascular disease, is characterized by functional deficits and apoptotic cell death. Autophagy, a type of programmed cell death, plays critical roles in controlling neuronal damage and metabolic homeostasis, and has been inextricably linked to cerebral ischemia. We previously identified a short peptide aptamer from collapsin response mediator protein 2 (CRMP2), designated the Ca2+ channel-binding domain 3 (CBD3) peptide, that conferred protection against excitotoxicity and traumatic brain injury. ST2-104, a nona-arginine (R9)-fused CBD3 peptide, exerted beneficial effects on neuropathic pain and was neuroprotective in a model of Alzheimer’s disease; however, the effect of ST2-104 on cerebral ischemia and its mechanism of action have not been studied. In this study, we modeled cerebral ischemia–reperfusion injury in rats with the middle cerebral artery occlusion (MCAO) as well as challenged SH-SY5Y neuroblastoma cells with glutamate to induce toxicity to interrogate the effects of ST2-104 on autophagy following ischemic/excitotoxic insults. ST2-104 reduced the infarct volume and improved the neurological score of rats subjected to MCAO. ST2-104 protected SH-SY5Y cells from death following glutamate exposure via blunting apoptosis and autophagy as well as limiting excessive calcium entry. 3-Methyladenine (3-MA), an inhibitor of autophagy, promoted the effects of ST2-104 in inhibiting apoptosis triggered by glutamate while rapamycin, an activator of autophagy, failed to do so. ST2-104 peptide reversed glutamate-induced apoptosis via inhibiting Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ)-mediated autophagy, which was partly enhanced by STO-609 (an inhibitor of CaMKKβ). ST2-104 attenuated neuronal apoptosis by inhibiting autophagy through CaMKKβ/AMPK/mTOR pathway. Our results suggest that the neuroprotective effect of ST2-104 are due to actions on the crosstalk between apoptosis and autophagy via the CaMKKβ/AMPK/mTOR signaling pathway. The findings present novel insights into the potential neuroprotection of ST2-104 in cerebral ischemia.
Establishment and characterization of patient-derived head and neck cancer models from surgical specimens and endoscopic biopsies
Authors: Strüder Daniel , Momper Theresa , Irmscher Nina , Krause Mareike , Liese Jan , Schraven Sebastian , Zimpfer Annette , Zonnur Sarah , Burmeister Ann-Sophie , Schneider Björn , Frerich Bernhard , Mlynski Robert , Große-Thie Christina , Junghanss Christian , Maletzki Claudia
Published: August 2021

Background

Head and neck squamous cell carcinoma (HNSCC) is heterogeneous in etiology, phenotype and biology. Patient-derived xenografts (PDX) maintain morphology and molecular profiling of the original tumors and have become a standard “Avatar” model for human cancer research. However, restricted availability of tumor samples hindered the widespread use of PDX. Most PDX-projects include only surgical specimens because reliable engraftment from biopsies is missing. Therefore, sample collection is limited and excludes recurrent and metastatic, non-resectable cancer from preclinical models as well as future personalized medicine.

Methods

This study compares the PDX-take rate, -growth, histopathology, and molecular characteristics of endoscopic specimens with surgical specimens. HNSCC samples (n = 55) were collected ad hoc, fresh frozen and implanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice.

Results

Engraftment was successful in both sample types. However, engraftment rate was lower (21 vs. 52%) and growth delayed (11.2 vs. 6.7 weeks) for endoscopic biopsies. Following engraftment, growth kinetic was similar. Comparisons of primary tumors and corresponding PDX models confirmed preservation of histomorphology (HE histology) and molecular profile (Illumina Cancer Hotspot Panel) of the patients’ tumors. Accompanying flow cytometry on primary tumor specimens revealed a heterogeneous tumor microenvironment among individual cases and identified M2-like macrophages as positive predictors for engraftment. Vice versa, a high PD-L1 expression (combined positive score on tumor/immune cells) predicted PDX rejection.

Conclusion

Including biopsy samples from locally advanced or metastatic lesions from patients with non-surgical treatment strategies, increases the availability of PDX for basic and translational research. This facilitates (pre-) clinical studies for individual response prediction based on immunological biomarkers.
Ribosomal L1 domain-containing protein 1 coordinates with HDM2 to negatively regulate p53 in human colorectal Cancer cells
Authors: Ding Li , Zhang Zhiping , Zhao Chenhong , Chen Lei , Chen Zhiqiang , Zhang Jie , Liu Yaxian , Nie Yesen , He Yanzhi , Liao Kai , Zhang Xinyue
Published: August 2021

Background

Ribosomal L1 domain-containing protein 1 (RSL1D1) is a nucleolar protein that is essential in cell proliferation. In the current opinion, RSL1D1 translocates to the nucleoplasm under nucleolar stress and inhibits the E3 ligase activity of HDM2 via direct interaction, thereby leading to stabilization of p53.

Methods

Gene knockdown was achieved in HCT116p53+/+, HCT116p53−/−, and HCT-8 human colorectal cancer (CRC) cells by siRNA transfection. A lentiviral expression system was used to establish cell strains overexpressing genes of interest. The mRNA and protein levels in cells were evaluated by qRT-PCR and western blot analyses. Cell proliferation, cell cycle, and cell apoptosis were determined by MTT, PI staining, and Annexin V-FITC/PI double staining assays, respectively. The level of ubiquitinated p53 protein was assessed by IP. The protein-RNA interaction was investigated by RIP. The subcellular localization of proteins of interest was determined by IFA. Protein-protein interaction was investigated by GST-pulldown, BiFC, and co-IP assays. The therapeutic efficacy of RSL1D1 silencing on tumor growth was evaluated in HCT116 tumor-bearing nude mice.

Results

RSL1D1 distributed throughout the nucleus in human CRC cells. Silencing of RSL1D1 gene induced cell cycle arrest at G1/S and cell apoptosis in a p53-dependent manner. RSL1D1 directly interacted with and recruited p53 to HDM2 to form a ternary RSL1D1/HDM2/p53 protein complex and thereby enhanced p53 ubiquitination and degradation, leading to a decrease in the protein level of p53. Destruction of the ternary complex increased the level of p53 protein. RSL1D1 also indirectly decreased the protein level of p53 by stabilizing HDM2 mRNA. Consequently, the negative regulation of p53 by RSL1D1 facilitated cell proliferation and survival and downregulation of RSL1D1 remarkably inhibited the growth of HCT116p53+/+ tumors in a nude mouse model.

Conclusion

We report, for the first time, that RSL1D1 is a novel negative regulator of p53 in human CRC cells and more importantly, a potential molecular target for anticancer drug development.
Optimizing gentamicin dosing in different pediatric age groups using population pharmacokinetics and Monte Carlo simulation
Authors: Ghoneim Ragia H. , Thabit Abrar K. , Lashkar Manar O. , Ali Ahmed S.
Published: August 2021

Introduction

The use of once daily dosing of aminoglycosides in pediatrics is increasing but studies on dose optimization targeting the pediatric population are limited. This study aimed to derive a population pharmacokinetic model of gentamicin and apply it to design optimal dosing regimens in pediatrics.

Methods

Population pharmacokinetics of gentamicin in pediatrics was described from a retrospective chart review of plasma gentamicin concentration data (peak/ trough levels) of pediatric patients (1 month − 12 years), admitted to non-critically ill pediatrics. Monte Carlo simulations were performed on the resulting pharmacokinetic model to assess the probability of achieving a Cmax/MIC target of 10 mg/L over a range of gentamicin MICs of 0.5–2 mg/L and once daily gentamicin dosing regimens. Results: A two-compartment model with additive residual error best described the model with weight incorporated as a significant covariate for both clearance and volume of distribution. Monte Carlo simulations demonstrated a good probability of target attainment even at a MIC of 2 mg/L, where neonates required doses of 6-7 mg/kg/day and older pediatrics required lower daily doses of 4–5 mg/kg/day while maintaining trough gentamicin concentration below the toxicity limit of 1 mg/L. Conclusion: Once daily dosing is a reasonable option in pediatrics that allows target attainment while maintaining trough gentamicin level below the limits of toxicity.
Understanding p53 tumour suppressor network
Authors: Panatta Emanuele , Zampieri Carlotta , Melino Gerry , Amelio Ivano
Published: August 2021

The mutation of TP53 gene affects half of all human cancers, resulting in impairment of the regulation of several cellular functions, including cell cycle progression and cell death in response to genotoxic stress. In the recent years additional p53-mediated tumour suppression mechanisms have been described, questioning the contribution of its canonical pathway for tumour suppression. These include regulation of alternative cell death modalities (i.e. ferroptosis), cell metabolism and the emerging role in RNA stability. Here we briefly summarize our knowledge on p53 “canonical DNA damage response” and discuss the most relevant recent findings describing potential mechanistic explanation of p53-mediated tumour suppression.
Impact of a medico-pharmaceutical follow-up and an optimized communication between hospital and community on the readmission to the emergency department for an adverse drug event: URGEIM, study protocol for a randomized controlled trial
Authors: Breuker Cyril , Faucanié Marie , Laureau Marion , Perier Damien , Pinzani Véronique , Marin Grégory , Sebbane Mustapha , Villiet M.
Published: August 2021

Background

Adverse drug events (ADE) represent one of the main causes of admission to emergency department (ED). Their detection, documentation, and reporting are essential to avoid readmission.

We hypothesize that a pharmacist-initiated multidisciplinary transition of care program combining ED pharmacist contribution and medications’ data transfer between inpatient and outpatient caregivers will reduce emergency visits related to ADE

Method/design

This is a prospective, open-label, randomized controlled trial. The primary aim of the study is 6-month ED readmission related to the same ADE. Three hundred forty-six adult patients with an ADE detected by a binomial pharmacist-physician will be recruited from the ED of an University Hospital and will be randomized in two groups: [1] experimental group (multidisciplinary transition of care program and medications’ data transfer between inpatient and outpatient caregivers) and [2] control group (usual care). Patients will be followed up over a period of 6 months. Endpoints will be carried out blindly of the randomization arm. The primary endpoint is the rate of patients who had at least one readmission in the ED for the same reason at 6 months (data collected during a phone call with the patient and the general practitioner). Trials registered NCT03725046.

Discussion

The trial results will have implications for the role of the clinical pharmacist in an emergency department. If successful, the intervention could be considered for implementation across other hospitals.

Trial registration

ClinicalTrials.govNCT03725046. Registered on 30 October 2018
Enhancement of biohydrogen production rate in Rhodospirillum rubrum by a dynamic CO-feeding strategy using dark fermentation
Authors: Rodríguez Alberto , Hernández-Herreros Natalia , García José L. , Auxiliadora Prieto M.
Published: August 2021

Background

Rhodospirillum rubrum is a purple non-sulphur bacterium that produces H2 by photofermentation of several organic compounds or by water gas-shift reaction during CO fermentation. Successful strategies for both processes have been developed in light-dependent systems. This work explores a dark fermentation bioprocess for H2 production from water using CO as the electron donor.

Results

The study of the influence of the stirring and the initial CO partial pressure (pCO) demonstrated that the process was inhibited at pCO of 1.00 atm. Optimal pCO value was established in 0.60 atm. CO dose adaptation to bacterial growth in fed-batch fermentations increased the global rate of H2 production, yielding 27.2 mmol H2 l−1 h−1 and reduced by 50% the operation time. A kinetic model was proposed to describe the evolution of the molecular species involved in gas and liquid phases in a wide range of pCO conditions from 0.10 to 1.00 atm.

Conclusions

Dark fermentation in R. rubrum expands the ways to produce biohydrogen from CO. This work optimizes this bioprocess at lab-bioreactor scale studying the influence of the stirring speed, the initial CO partial pressure and the operation in batch and fed-batch regimes. Dynamic CO supply adapted to the biomass growth enhances the productivity reached in darkness by other strategies described in the literature, being similar to that obtained under light continuous syngas fermentations. The kinetic model proposed describes all the conditions tested.
A loop-mediated isothermal amplification assay for Schistosoma mansoni detection in Biomphalaria spp. from schistosomiasis-endemic areas in Minas Gerais, Brazil
Authors: Mesquita Silvia Gonçalves , Neves Floria Gabriela dos Santos , Scholte Ronaldo Guilherme Carvalho , Carvalho Omar dos Santos , Fonseca Cristina Toscano , Caldeira Roberta Lima
Published: August 2021

Background

Schistosomiasis a neglected tropical disease  endemic in Brazil. It is caused by the trematode Schistosoma mansoni, which is transmitted by snails of the genus Biomphalaria. Among measures used to control and eliminate schistosomiasis, accurate mapping and monitoring of snail breeding sites are recommended. Despite the limitations of parasitological methods, they are still used to identify infected snails. Loop-mediated isothermal amplification (LAMP) is a sensitive, rapid, and cost-effective diagnostic method for the identification of infected snails. In the work reported here, we aimed to validate the use of LAMP for the detection of S. mansoni in snails of the genus Biomphalaria.

Methods

Snails were collected in five municipalities of the Mucuri Valley and Jequitinhonha Valley regions in the state of Minas Gerais, Brazil. Snails were pooled according to collection site and then squeezed for the detection of S. mansoni and other trematode larvae. Pooled snails were subjected to pepsin digestion and DNA extraction. Molecular assays were performed for species-specific identification and characterization of the samples. A previously described LAMP assay was adapted, evaluated, and validated using laboratory and field samples.

Results

Using the parasitological method described here, S. mansoni cercariae were detected in snails from two collection sites, and cercariae of the family Spirorchiidae were found in snails from one site. The snails were identified by polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP). Biomphalaria glabrata, the main snail host of S. mansoni in Brazil, was detected in 72.2% of the collection sites. Biomphalaria kuhniana, which is resistant to S. mansoni infection, was found in the remaining sites. Multiplex, low stringency (LS), and conventional PCR allowed the detection of positive snails in four additional sites. Trematodes belonging to the families Strigeidae and Echinostomatidae were detected by multiplex PCR in two sites. The LAMP assay was effective in detecting the presence of S. mansoni infection in laboratory (7 days post-infection) and field samples with no cross-reactivity for other trematodes. When compared to LS and conventional PCR, LAMP showed 100% specificity, 85.7% sensitivity, and a κ index of 0.88.

Conclusions

Our findings suggest that LAMP is a good alternative method for the detection and monitoring of transmission foci of S. mansoni, as it was three times as effective as the parasitological examination used here for the detection of infection, and is more directly applicable in the field than other molecular techniques.

Graphical abstract
Recombination and lineage-specific mutations linked to the emergence of SARS-CoV-2
Authors: Patiño-Galindo Juan Ángel , Filip Ioan , Chowdhury Ratul , Maranas Costas D. , Sorger Peter K. , AlQuraishi Mohammed , Rabadan Raul
Published: August 2021

Background

The emergence of SARS-CoV-2 underscores the need to better understand the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. In the betacoronavirus genus, which also includes SARS-CoV and MERS-CoV, recombination frequently encompasses the receptor binding domain (RBD) of the Spike protein, which is responsible for viral binding to host cell receptors. In this work, we reconstruct the evolutionary events that have accompanied the emergence of SARS-CoV-2, with a special emphasis on the RBD and its adaptation for binding to its receptor, human ACE2.

Methods

By means of phylogenetic and recombination analyses, we found evidence of a recombination event in the RBD involving ancestral linages to both SARS-CoV and SARS-CoV-2. We then assessed the effect of this recombination at protein level by reconstructing the RBD of the closest ancestors to SARS-CoV-2, SARS-CoV, and other Sarbecoviruses, including the most recent common ancestor of the recombining clade. The resulting information was used to measure and compare, in silico, their ACE2-binding affinities using the physics-based trRosetta algorithm.

Results

We show that, through an ancestral recombination event, SARS-CoV and SARS-CoV-2 share an RBD sequence that includes two insertions (positions 432-436 and 460-472), as well as the variants 427N and 436Y. Both 427N and 436Y belong to a helix that interacts directly with the human ACE2 (hACE2) receptor. Reconstruction of ancestral states, combined with protein-binding affinity analyses, suggests that the recombination event involving ancestral strains of SARS-CoV and SARS-CoV-2 led to an increased affinity for hACE2 binding and that alleles 427N and 436Y significantly enhanced affinity as well.

Conclusions

We report an ancestral recombination event affecting the RBD of both SARS-CoV and SARS-CoV-2 that was associated with an increased binding affinity to hACE2. Structural modeling indicates that ancestors of SARS-CoV-2 may have acquired the ability to infect humans decades ago. The binding affinity with the human receptor would have been subsequently boosted in SARS-CoV and SARS-CoV-2 through further mutations in RBD.
Delayed functional therapy after acute lateral ankle sprain increases subjective ankle instability – the later, the worse: a retrospective analysis
Authors: Raeder Christian , Tennler Janina , Praetorius Arthur , Ohmann Tobias , Schoepp Christian
Published: August 2021

Background

The lateral ankle sprain (LAS) is one of the most common injuries in everyday and sports activities. Approximately 20–40 % of patients with LAS develop a chronic ankle instability (CAI). The underlying mechanisms for CAI have not yet been clearly clarified. An inadequate rehabilitation after LAS can be speculated, since the LAS is often handled as a minor injury demanding less treatment. Therefore, the aims of this retrospective study were to determine the CAI rate depending on age and sex and to identify possible determinants for developing CAI.

Methods

Between 2015 and 2018 we applied the diagnostic code “sprain of ankle” (ICD S93.4) to identify relevant cases from the database of the BG Klinikum Duisburg, Germany. Patients received a questionnaire containing the Tegner-Score, the Cumberland Ankle Instability Tool (CAIT) and the Foot and Ankle Disability Index. Additionally, there were questions about the modality and beginning of therapy following LAS and the number of recurrent sprains. There was a total of 647 completed datasets. These were divided into a CAI and non-CAI group according to a CAIT cut-off-score with CAI ≤ 24 and non-CAI > 24 points, representing one out of three criteria for having CAI based on international consensus.

Results

The overall CAI rate was 17.3 %. We identified a higher CAI rate in females and within the age segment of 41 to 55 years. A later start of therapy (> 4 weeks) after acute LAS significantly increases ankle instability in CAIT (p < .05). There was a significantly higher CAIT score in patients having no recurrent sprain compared to patients having 1–3 recurrent sprains or 4–5 recurrent sprains (p < .001).

Conclusions

Females over 41 years show a higher CAI rate which implies to perform specific prevention programs improving ankle function following acute LAS. A delayed start of therapy seems to be an important determinant associated with the development of CAI. Another contributing factor may be a frequent number of recurrent sprains that are also linked to greater levels of subjective ankle instability. Therefore, we would recommend an early start of functional therapy after acute LAS in the future to minimize the development of CAI.
MPDB 2.0: a large scale and integrated medicinal plant database of Bangladesh
Authors: Hussain Nazmul , Chanda Rony , Abir Ruhshan Ahmed , Mou Mohsina Akter , Hasan Md. Kamrul , Ashraf M. Arif
Published: August 2021

Objective

MPDB 2.0 is built to be the continuation of MPDB 1.0, to serve as a more comprehensive data repertoire for Bangladeshi medicinal plants, and to provide a user-friendly interface for researchers, health practitioners, drug developers, and students who wish to study the various medicinal & nutritive plants scattered around Bangladesh and the underlying phytochemicals contributing to their efficacy in Bangladeshi folk medicine.

Results

MPDB 2.0 database (https://www.medicinalplantbd.com/) comprises a collection of more than five hundred Bangladeshi medicinal plants, alongside a record of their corresponding scientific, family, and local names together with their utilized parts, information regarding ailments, active compounds, and PubMed ID of related publications. While medicinal plants are not limited to the borders of any country, Bangladesh and its Southeast Asian neighbors do boast a huge collection of potent medicinal plants with considerable folk-medicinal history compared to most other countries in the world. Development of MPDB 2.0 has been highly focused upon human diseases, albeit many of the plants indexed here can serve in developing biofuel (e.g.: Jatropha curcas used in biofuel) or bioremediation technologies (e.g.: Amaranthus cruentus helps to reduce cadmium level in soil) or nutritive diets (Terminalia chebula can be used in nutritive diets) or cosmetics (Aloe vera used in cosmetics), etc.
Acute kidney injury prevalence, progression and long-term outcomes in critically ill patients with COVID-19: a cohort study
Authors: Lumlertgul Nuttha , Pirondini Leah , Cooney Enya , Kok Waisun , Gregson John , Camporota Luigi , Lane Katie , Leach Richard , Ostermann Marlies
Published: August 2021

Background

There are limited data on acute kidney injury (AKI) progression and long-term outcomes in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to describe the prevalence and risk factors for development of AKI, its subsequent clinical course and AKI progression, as well as renal recovery or dialysis dependence and survival in this group of patients.

Methods

This was a retrospective observational study in an expanded tertiary care intensive care unit in London, United Kingdom. Critically ill patients admitted to ICU between 1st March 2020 and 31st July 2020 with confirmed SARS-COV2 infection were included. Analysis of baseline characteristics, organ support, COVID-19 associated therapies and their association with mortality and outcomes at 90 days was performed.

Results

Of 313 patients (70% male, mean age 54.5 ± 13.9 years), 240 (76.7%) developed AKI within 14 days after ICU admission: 63 (20.1%) stage 1, 41 (13.1%) stage 2, 136 (43.5%) stage 3. 113 (36.1%) patients presented with AKI on ICU admission. Progression to AKI stage 2/3 occurred in 36%. Risk factors for AKI progression were mechanical ventilation [HR (hazard ratio) 4.11; 95% confidence interval (CI) 1.61–10.49] and positive fluid balance [HR 1.21 (95% CI 1.11–1.31)], while steroid therapy was associated with a reduction in AKI progression (HR 0.73 [95% CI 0.55–0.97]). Kidney replacement therapy (KRT) was initiated in 31.9%. AKI patients had a higher 90-day mortality than non-AKI patients (34% vs. 14%;p < 0.001). Dialysis dependence was 5% at hospital discharge and 4% at 90 days. Renal recovery was identified in 81.6% of survivors at discharge and in 90.9% at 90 days. At 3 months, 16% of all AKI survivors had chronic kidney disease (CKD); among those without renal recovery, the CKD incidence was 44%.

Conclusions

During the first COVID-19 wave, AKI was highly prevalent among severely ill COVID-19 patients with a third progressing to severe AKI requiring KRT. The risk of developing CKD was high. This study identifies factors modifying AKI progression, including a potentially protective effect of steroid therapy. Recognition of risk factors and monitoring of renal function post-discharge might help guide future practice and follow-up management strategies.

Trial registrationNCT04445259
Downlink multi-user algorithms for millimeter-wave wideband linear arrays on PD-NOMA-based squint steering beams
Authors: Pan Xiaoliang , Yang Luxi
Published: August 2021

This article investigates using a phased linear antenna array instead of the planar array to circumvent the problem that two frequency squint steering main beams cannot cover any two beam directions simultaneously. First, we approximate the donut-shaped main beam of the linear array by means of multiple pencil-shaped main beams of a virtual planar array for matching the steering main beam of the linear array with the multi-path sparse scattering channel model mathematically and give a method for calculating the number of antenna elements of the virtual array. Second, we cope with possible inter-user interference on a single squint main beam of the linear array in some scenarios by means of the power-domain non-orthogonal multiple access (PD-NOMA) technique, making it possible to support communication with two users on a single squint main beam at the base station (BS) side. The feasible domain of PD-NOMA is given when a single antenna is used for both the BS and the user end, assuming a two-user successive interference cancellation (SIC) decoding power ratio limit. Third, three algorithms are given for serving multi-user at the BS via squint beams of the linear array. Finally, numerical results show that the second proposed algorithm supporting PD-NOMA pairing within a single donut-shaped squint main beam significantly increases the number of simultaneous users served within a single cellular system.
Well posedness of a nonlinear mixed problem for a parabolic equation with integral condition
Authors: Djerad Abdelkader , Memou Ameur , Hameida Ali
Published: August 2021

The aim of this work is to prove the well posedness of some posed linear and nonlinear mixed problems with integral conditions. First, an a priori estimate is established for the associated linear problem and the density of the operator range generated by the considered problem is proved by using the functional analysis method. Subsequently, by applying an iterative process based on the obtained results for the linear problem, the existence, uniqueness of the weak solution of the nonlinear problems is established.
Type 1 diabetes in pregnancy is associated with distinct changes in the composition and function of the gut microbiome
Authors: Roth-Schulze Alexandra J. , Penno Megan A. S. , Ngui Katrina M. , Oakey Helena , Bandala-Sanchez Esther , Smith Alannah D. , Allnutt Theo R. , Thomson Rebecca L. , Vuillermin Peter J. , Craig Maria E. , Rawlinson William D. , Davis Elizabeth A. , Harris Mark , Soldatos Georgia , Colman Peter G. , Wentworth John M. , Haynes Aveni , Barry Simon C. , Sinnott Richard O. , Morahan Grant , Bediaga Naiara G. , Smyth Gordon K. , Papenfuss Anthony T. , Couper Jennifer J. , Harrison Leonard C. ,   on behalf of the ENDIA Study Group
Published: August 2021

Background

The gut microbiome changes in response to a range of environmental conditions, life events and disease states. Pregnancy is a natural life event that involves major physiological adaptation yet studies of the microbiome in pregnancy are limited and their findings inconsistent. Pregnancy with type 1 diabetes (T1D) is associated with increased maternal and fetal risks but the gut microbiome in this context has not been characterized. By whole metagenome sequencing (WMS), we defined the taxonomic composition and function of the gut bacterial microbiome across 70 pregnancies, 36 in women with T1D.

Results

Women with and without T1D exhibited compositional and functional changes in the gut microbiome across pregnancy. Profiles in women with T1D were distinct, with an increase in bacteria that produce lipopolysaccharides and a decrease in those that produce short-chain fatty acids, especially in the third trimester. In addition, women with T1D had elevated concentrations of fecal calprotectin, a marker of intestinal inflammation, and serum intestinal fatty acid-binding protein (I-FABP), a marker of intestinal epithelial damage.

Conclusions

Women with T1D exhibit a shift towards a more pro-inflammatory gut microbiome during pregnancy, associated with evidence of intestinal inflammation. These changes could contribute to the increased risk of pregnancy complications in women with T1D and are potentially modifiable by dietary means.
A generalized Fourier transform by means of change of variables within multilinear approximation
Authors: Chevreuil Mathilde , Slama Myriam
Published: August 2021

The paper deals with approximations of periodic functions that play a significant role in harmonic analysis. The approach revisits the trigonometric polynomials, seen as combinations of functions, and proposes to extend the class of models of the combined functions to a wider class of functions. The key here is to use structured functions, that have low complexity, with suitable functional representation and adapted parametrizations for the approximation. Such representation enables to approximate multivariate functions with few eventually random samples. The new parametrization is determined automatically with a greedy procedure, and a low rank format is used for the approximation associated with each new parametrization. A supervised learning algorithm is used for the approximation of a function of multiple random variables in tree-based tensor format, here the particular Tensor Train format. Adaptive strategies using statistical error estimates are proposed for the selection of the underlying tensor bases and the ranks for the Tensor-Train format. The method is applied for the estimation of the wall pressure for a flow over a cylinder for a range of low to medium Reynolds numbers for which we observe two flow regimes: a laminar flow with periodic vortex shedding and a laminar boundary layer with a turbulent wake (sub-critic regime). The automatic re-parametrization enables here to take into account the specific periodic feature of the pressure.
Monocyte-to-lymphocyte ratio is associated with 28-day mortality in patients with acute respiratory distress syndrome: a retrospective study
Authors: Yang Lijuan , Gao Chang , Li Fengyuan , Yang Ling , Chen Jiahao , Guo Shiqi , He Ying , Guo Qiang
Published: August 2021

Background

Systemic inflammation relates to the initiation and progression of acute respiratory distress syndrome (ARDS). Neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW)/albumin ratio have been reported to be predictive prognostic biomarkers in ARDS patients. However, the role of monocyte-to-lymphocyte ratio (MLR) as a prognostic inflammatory biomarker in a variety of diseases is rarely mentioned in ARDS. In this study, we explored the relationship between MLR and disease severity in ARDS patients and compared it with other indicators associated with 28-day mortality in patients with ARDS.

Methods

We retrospectively included 268 patients who fulfilled the Berlin definition of ARDS and were admitted to a single institute from 2016 to 2020. Clinical characteristics and experimental test data were collected from medical records within 24 h after the ARDS diagnosis. MLR, NLR, and RDW/albumin ratio levels were calculated. The primary clinical outcome was 28-day mortality. Logistic regression analysis was used to illustrate the relationship between indicators and 28-day mortality. Receiver operating characteristic (ROC) curve was used to evaluate the area under the curve (AUC), and propensity score matching (PSM) was employed to validate our findings.

Results

The median MLR values were higher for non-survivors than for survivors before and after matching (P<0.001, P=0.001, respectively). MLR values were significantly associated with 28-day mortality (OR 2.956; 95% CI 1.873–4.665; P<0.001). MLR and NLR indicators were combined for predictive efficacy analysis, and its AUC reached 0.750. There was a significant increase in 28-day mortality depending on the increasing MLR level: low MLR group 38 (20.4%), high MLR group 47 (57.3%) (P<0.001).

Conclusions

Higher MLR values were associated with 28-day mortality in patients with ARDS. Further investigation is required to verify this relationship with prospectively collected data.