bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrin α2β1-targeting ferritin nanocarrier traverses the blood–brain barrier for effective glioma chemotherapy
Authors: Huang Chiun-Wei , Chuang Chia-Pao , Chen Yan-Jun , Wang Hsu-Yuan , Lin Jia-Jia , Huang Chiung-Yin , Wei Kuo-Chen , Huang Feng-Ting
Published: June 2021

Background

Ferritin, the natural iron storage protein complex, self-assembles into a uniform cage-like structure. Human H-ferritin (HFn) has been shown to transverse the blood–brain barrier (BBB) by binding to transferrin receptor 1 (TfR1), which is abundant in endothelial cells and overexpressed in tumors, and enters cells via endocytosis. Ferritin is easily genetically modified with various functional molecules, justifying that it possesses great potential for development into a nanocarrier drug delivery system.

Results

In this study, a unique integrin α2β1-targeting H-ferritin (2D-HFn)-based drug delivery system was developed that highlights the feasibility of receptor-mediated transcytosis (RMT) for glioma tumor treatment. The integrin targeting α2β1 specificity was validated by biolayer interferometry in real time monitoring and followed by cell binding, chemo-drug encapsulation stability studies. Compared with naïve HFn, 2D-HFn dramatically elevated not only doxorubicin (DOX) drug loading capacity (up to 458 drug molecules/protein cage) but also tumor targeting capability after crossing BBB in an in vitro transcytosis assay (twofold) and an in vivo orthotopic glioma model. Most importantly, DOX-loaded 2D-HFn significantly suppressed subcutaneous and orthotopic U-87MG tumor progression; in particular, orthotopic glioma mice survived for more than 80 days.

Conclusions

We believe that this versatile nanoparticle has established a proof-of-concept platform to enable more accurate brain tumor targeting and precision treatment arrangements. Additionally, this unique RMT based ferritin drug delivery technique would accelerate the clinical development of an innovative drug delivery strategy for central nervous system diseases with limited side effects in translational medicine.

Graphic Abstract
Enabling patient-reported outcome measures in clinical trials, exemplified by cardiovascular trials
Authors: Coles Theresa M. , Hernandez Adrian F. , Reeve Bryce B. , Cook Karon , Edwards Michael C. , Boutin Marc , Bush Elizabeth , Degboe Arnold , Roessig Lothar , Rudolph Amy , McNulty Pauline , Patel Nikunj , Kay-Mugford Trish , Vernon Margaret , Woloschak Michael , Buchele Gustavo , Spertus John A. , Roe Matthew T. , Bury Denise , Weinfurt Kevin
Published: June 2021

Objectives

There has been limited success in achieving integration of patient-reported outcomes (PROs) in clinical trials. We describe how stakeholders envision a solution to this challenge.

Methods

Stakeholders from academia, industry, non-profits, insurers, clinicians, and the Food and Drug Administration convened at a Think Tank meeting funded by the Duke Clinical Research Institute to discuss the challenges of incorporating PROs into clinical trials and how to address those challenges. Using examples from cardiovascular trials, this article describes a potential path forward with a focus on applications in the United States.

Results

Think Tank members identified one key challenge: a common understanding of the level of evidence that is necessary to support patient-reported outcome measures (PROMs) in trials. Think Tank participants discussed the possibility of creating general evidentiary standards depending upon contextual factors, but such guidelines could not be feasibly developed because many contextual factors are at play. The attendees posited that a more informative approach to PROM evidentiary standards would be to develop validity arguments akin to courtroom briefs, which would emphasize a compelling rationale (interpretation/use argument) to support a PROM within a specific context. Participants envisioned a future in which validity arguments would be publicly available via a repository, which would be indexed by contextual factors, clinical populations, and types of claims.

Conclusions

A publicly available repository would help stakeholders better understand what a community believes constitutes compelling support for a specific PROM in a trial. Our proposed strategy is expected to facilitate the incorporation of PROMs into cardiovascular clinical trials and trials in general.
Sonication fluid culture of antibiotic-loaded bone cement spacer has high accuracy to confirm eradication of infection before reimplantation of new prostheses
Authors: Zhang Qingyu , Ding Baocong , Wu Jinglin , Dong Jun , Liu Fanxiao
Published: June 2021

Background

Sonication fluid culture of antibiotic-loaded bone cement spacer has been used to predict reinfection of two-stage revision, but its value remains disputable. This study aims to evaluate the association between the culture result of the sonicated spacer and the status of patients with periprosthetic joint infection receiving two-stage revision.

Materials and methods

A comprehensive electronic literature search was performed through four databases including PubMed, Embase/Ovid, and EBSCO, and the Cochrane Library to retrieve studies in which sonication fluid culture of the antibiotic spacer was conducted before reimplantation. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the association between the culture result of sonicated spacer and prognosis of the two-stage revision.

Results

Eleven eligible studies comprising 603 artificial joints with PJI (134 suffering a clinical failure of two-stage revision) were included in the quantitative analysis. The pooled incidences of positive culture of sonicated spacer and intraoperative tissue were 0.14 (95% confidence interval [CI] 0.08–0.21) and 0.14 (95% CI 0.08–0.20), respectively. A positive culture of sonicated antibiotic-loaded bone cement spacer illustrated moderate sensitivity (0.31, 95% CI 0.13–0.58) but high specificity (0.94, 95% CI 0.86–0.98) for the diagnosis of therapeutic failure of two-stage revision; the pooled DOR was 7.67 (95% CI, 3.63–16.22). Meanwhile, the pooled sensitivity, specificity, and DOR of intraoperative tissue culture during the two-stage revision to predict therapeutic failure were 0.32 (95% CI, 0.20–0.47), 0.96 (95% CI, 0.92–0.98), and 10.62 (95% CI, 4.90–23.01), respectively.

Conclusions

Sonication fluid culture of antibiotic-loaded bone cement spacer revealed high accuracy for confirming eradication of infection before reimplantation of new prostheses and therefore could be used as a supplement for assessing therapeutic effect for PJI. However, both sonication fluid culture and intraoperative tissue culture from antibiotic-loaded bone cement spacer showed restricted yield for the prediction of a septic failure after the two-stage revision of PJI. Large-scale, prospective studies are still needed to testify current findings.
High-throughput surface marker screen on primary human breast tissues reveals further cellular heterogeneity
Authors: Virtanen Siru , Schulte Reiner , Stingl John , Caldas Carlos , Shehata Mona
Published: June 2021

Background

Normal human breast tissues are a heterogeneous mix of epithelial and stromal subtypes in different cell states. Delineating the spectrum of cellular heterogeneity will provide new insights into normal cellular properties within the breast tissue that might become dysregulated in the initial stages of cancer. Investigation of surface marker expression provides a valuable approach to resolve complex cell populations. However, the majority of cell surface maker expression of primary breast cells have not been investigated.

Methods

To determine the differences in expression of a range of uninvestigated cell surface markers between the normal breast cell subpopulations, primary human breast cells were analysed using high-throughput flow cytometry for the expression of 242 cell surface proteins in conjunction with EpCAM/CD49f staining.

Results

We identified 35 surface marker proteins expressed on normal breast epithelial and/or stromal subpopulations that were previously unreported. We also show multiple markers were equally expressed in all cell populations (e.g. CD9, CD59, CD164) while other surface markers were confirmed to be enriched in different cell lineages: CD24, CD227 and CD340 in the luminal compartment, CD10 and CD90 in the basal population, and CD34 and CD140b on stromal cells.

Conclusions

Our dataset of CD marker expression in the normal breast provides better definition for breast cellular heterogeneity.
Leveraging breeding programs and genomic data in Norway spruce (Picea abies L. Karst) for GWAS analysis
Authors: Chen Zhi-Qiang , Zan Yanjun , Milesi Pascal , Zhou Linghua , Chen Jun , Li Lili , Cui BinBin , Niu Shihui , Westin Johan , Karlsson Bo , García-Gil Maria Rosario , Lascoux Martin , Wu Harry X.
Published: June 2021

Background

Genome-wide association studies (GWAS) identify loci underlying the variation of complex traits. One of the main limitations of GWAS is the availability of reliable phenotypic data, particularly for long-lived tree species. Although an extensive amount of phenotypic data already exists in breeding programs, accounting for its high heterogeneity is a great challenge. We combine spatial and factor-analytics analyses to standardize the heterogeneous data from 120 field experiments of 483,424 progenies of Norway spruce to implement the largest reported GWAS for trees using 134 605 SNPs from exome sequencing of 5056 parental trees.

Results

We identify 55 novel quantitative trait loci (QTLs) that are associated with phenotypic variation. The largest number of QTLs is associated with the budburst stage, followed by diameter at breast height, wood quality, and frost damage. Two QTLs with the largest effect have a pleiotropic effect for budburst stage, frost damage, and diameter and are associated with MAP3K genes. Genotype data called from exome capture, recently developed SNP array and gene expression data indirectly support this discovery.

Conclusion

Several important QTLs associated with growth and frost damage have been verified in several southern and northern progeny plantations, indicating that these loci can be used in QTL-assisted genomic selection. Our study also demonstrates that existing heterogeneous phenotypic data from breeding programs, collected over several decades, is an important source for GWAS and that such integration into GWAS should be a major area of inquiry in the future.
Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes
Authors: Tan Liqiang , Cheng Weisheng , Liu Fang , Wang Dan Ohtan , Wu Linwei , Cao Nan , Wang Jinkai
Published: June 2021

Background

Canonical nonsense-mediated decay (NMD) is an important splicing-dependent process for mRNA surveillance in mammals. However, processed pseudogenes are not able to trigger NMD due to their lack of introns. It is largely unknown whether they have evolved other surveillance mechanisms.

Results

Here, we find that the RNAs of pseudogenes, especially processed pseudogenes, have dramatically higher m6A levels than their cognate protein-coding genes, associated with de novo m6A peaks and motifs in human cells. Furthermore, pseudogenes have rapidly accumulated m6A motifs during evolution. The m6A sites of pseudogenes are evolutionarily younger than neutral sites and their m6A levels are increasing, supporting the idea that m6A on the RNAs of pseudogenes is under positive selection. We then find that the m6A RNA modification of processed, rather than unprocessed, pseudogenes promotes cytosolic RNA degradation and attenuates interference with the RNAs of their cognate protein-coding genes. We experimentally validate the m6A RNA modification of two processed pseudogenes,DSTNP2andNAP1L4P1, which promotes the RNA degradation of both pseudogenes and their cognate protein-coding genesDSTNandNAP1L4. In addition, the m6A ofDSTNP2regulation of DSTN is partially dependent on the miRNA miR-362-5p.

Conclusions

Our discovery reveals a novel evolutionary role of m6A RNA modification in cleaning up the unnecessary processed pseudogene transcripts to attenuate their interference with the regulatory network of protein-coding genes.
Early onset of pre-lethal effects of lotilaner (Credelio®) on Amblyomma americanum ticks on experimentally infested dogs
Authors: Wenger Martha J. , Kollasch Todd M. , Burke Madeline C. , Jones Livvy , Locklear Casey , Hedberg Makaela , Miller Lauren , Reeves Sydnie , Ritchie Debra , Rumschlag Anthony J. , Ryan William G. , Smith Vicki , Sutherland Cameron , Reif Kathryn E. , Herrin Brian H.
Published: June 2021

Background

The speed with which acaricides paralyze and kill ticks is relevant to impeding pathogen transmission. The objective of this study was to assess early-onset lotilaner effects on the motility and weights of Amblyomma americanum ticks collected from treated dogs.

Methods

Twelve healthy dogs were randomized between two groups to receive either lotilaner (Credelio®) on Day 0 or to be sham treated. On Day 7, 25 male and 25 female A. americanum were placed under bandages, two on each flank of each dog. After 30 or 45 min, all unattached ticks were removed and T = 0 was set. At T = 2, 4, 8 and 24 h post attachment, 5 attached ticks removed from each bandage on each dog were weighed, assessed by blinded observers for righting ability and movement recorded.

Results

After the infestation period significantly fewer treated than control dogs had 20 ticks attached (50.0% versus 91.7%, P = 0.0015). At 24 h post attachment, mean weights of ticks from treated dogs (males 1.69 mg; females 2.72) were significantly less than ticks from controls (males 2.66 mg; females 4.67) (Pmale = 0.0002; Pfemale < 0.0001). Mean tick weights from the treated group were significantly lower at 24 h than at earlier time points (Pmale < 0.0307; Pfemale = 0.0021). At 4 and 8 h, significantly fewer ticks from treated (14.3%, 0.0%, respectively) than from control dogs could right (73.3%, 70.0%) (P4h < 0.0001; P8h = 0.0024) (at 24 h, all ticks from treated dogs were dead), and distance moved was significantly less at all time points (P2h = 0.0413; P4h, P8h < 0.0001). Mean and maximum velocity of ticks from treated dogs were significantly lower, relative to controls, at 4 and 8 h (P ≤ 0.0001). Within the treated group, collected ticks had significantly lower mean and maximum velocities at 4 and 8 h compared to 2 h (Pmean < 0.0042; Pmax < 0.0194).

Conclusion

The observed changes indicate that lotilaner may disrupt tick attachment. In ticks that attached, a progressive impairment of neuromuscular processes began within 2 h. Those irreversible changes could substantially reduce the risk of pathogen transmission from tick to host.

Graphical Abstract
Effect of omalizumab for autoimmune progesterone dermatitis refractory to bilateral oophorectomy: a case report
Authors: Varghese Akshay , Paul Terri , Kim Harold , Van Uum Stan , Vadas Peter , Azzola Alescia
Published: June 2021

Background

Autoimmune progesterone dermatitis (APD) is a rare skin condition caused by sensitivity to high levels of progesterone secreted during the luteal phase of the menstrual cycle. This may be due to various pathophysiological mechanisms including a Type I and Type IV hypersensitivity reaction. Here we present the case of a patient with APD whose episodic flares were controlled by the addition of omalizumab, after a bilateral oophorectomy failed to resolve her symptoms.

Case Presentation

A 34-year-old female presented to our Endocrine clinic with marked Cushingoid features secondary to high-dose oral prednisone prescribed for APD diagnosed 6 years earlier. She first developed a pruritic maculopapular rash on her arms and legs just after the birth of her second child in 2009. The rash was also associated with headaches and diffuse angioedema. Symptoms occurred for 1–2 weeks, in a cyclical fashion, during the luteal phase of each menstrual cycle and subsided within a few days after menses. The severity of symptoms increased as time went on, and flare-ups began to also include dyspnea, nausea, vomiting and abdominal pain. Her symptoms improved with administration of oral prednisone, but she continued to experience breakthrough symptoms. After multiple failed treatment modalities, she elected bilateral oophorectomy in 2018. However, her symptoms of APD persisted and she still required high-dose oral prednisone. Her condition was further complicated by vasomotor menopausal symptoms and progressive iatrogenic Cushing’s syndrome. She eventually was started on Omalizumab, which suppressed further recurrences of APD symptoms and allowed her to wean off prednisone. Vasomotor menopausal symptoms responded well to the addition of conjugated estrogens with bazedoxifene. However, her symptoms of diffuse bony pain and arthralgias which started whilst on prednisone have persisted in spite of discontinuing prednisone.

Conclusions

To our knowledge, this is only the third case of APD which was successfully treated with Omalizumab and the first case where a bilateral oophorectomy failed to resolve symptoms of APD in the literature. This case also demonstrates the complications of vasomotor menopausal symptoms secondary to a bilateral oophorectomy, as well as the adverse effects of long-term glucocorticoid therapy.
[99mTc]Tc-Galacto-RGD2 integrin αvβ3-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data
Authors: Fu Jingjing , Xie Yan , Fu Tong , Qiu Fan , Yu Fei , Qu Wei , Yao Xiaochen , Zhang Aiping , Yang Zhenhua , Shao Guoqiang , Meng Qingle , Shi Xiumin , Huang Yue , Gu Wei , Wang Feng
Published: June 2021

Background

Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of [99mTc]Tc-Galacto-RGD2 single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, integrin αvβ3 expression, and neovascularization in lung cancer subtypes was also addressed.

Methods

A total of 185 patients with lung cancer and 25 patients with benign lung diseases were enrolled in this prospective study from January 2013 to December 2016. All patients underwent [99mTc]Tc-Galacto-RGD2 imaging. The region of interest was drawn around each primary lesion, and tumour uptake of [99mTc]Tc-Galacto-RGD2 was expressed as the tumour/normal tissue ratio(T/N). The diagnostic efficacy was evaluated by receiver operating characteristic curve analysis. Tumour specimens were obtained from 66 patients with malignant diseases and 7 with benign disease. Tumour expression levels of αvβ3, CD31, Ki-67, and CXCR4 were further analysed for the evaluation of biological behaviours.

Results

The lung cancer patients included 22 cases of small cell lung cancer (SCLC), 48 squamous cell carcinoma (LSC), 97 adenocarcinoma (LAC), and 18 other types of lung cancer. The sensitivity, specificity, and accuracy of [99mTc]Tc-Galacto-RGD2 SPECT/CT using a cut-off value of T/N ratio at 2.5 were 91.89%, 48.0%, and 86.67%, respectively. Integrin αvβ3 expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αvβ3 expression. Integrin αvβ3 expression levels were significantly higher in advanced (III, IV) than early stages (I, II). However, there was no significant correlation between tumour uptake and αvβ3 expression.

Conclusions

[99mTc]Tc-Galacto-RGD2 SPECT/CT has high sensitivity but limited specificity for detecting primary lung cancer, integrin expression in the tumour vessel and tumour cell membrane contributes to the tumour uptake.
Drosophila, a powerful model to study virus-host interactions and pathogenicity in the fight against SARS-CoV-2
Authors: van de Leemput Joyce , Han Zhe
Published: June 2021

The COVID-19 pandemic is having a tremendous impact on humanity. Although COVID-19 vaccines are showing promising results, they are not 100% effective and resistant mutant SARS-CoV-2 strains are on the rise. To successfully fight against SARS-CoV-2 and prepare for future coronavirus outbreaks, it is essential to understand SARS-CoV-2 protein functions, their host interactions, and how these processes convey pathogenicity at host tissue, organ and systemic levels. In vitro models are valuable but lack the physiological context of a whole organism. Current animal models for SARS-CoV-2 research are exclusively mammals, with the intrinsic limitations of long reproduction times, few progeny, ethical concerns and high maintenance costs. These limitations make them unsuitable for rapid functional investigations of virus proteins as well as genetic and pharmacological screens. Remarkably, 90% of the SARS-CoV-2 virus-host interacting proteins are conserved between Drosophila and humans. As a well-established model system for studying human diseases, the fruit fly offers a highly complementary alternative to current mammalian models for SARS-CoV-2 research, from investigating virus protein function to developing targeted drugs. Herein, we review Drosophila’s track record in studying human viruses and discuss the advantages and limitations of using fruit flies for SARS-CoV-2 research. We also review studies that already used Drosophila to investigate SARS-CoV-2 protein pathogenicity and their damaging effects in COVID-19 relevant tissues, as well as studies in which the fly was used as an efficient whole animal drug testing platform for targeted therapeutics against SARS-CoV-2 proteins or their host interacting pathways.
Tracking progress in anthropometric failure among under-five children in Ethiopia: a geospatial and multilevel analysis
Authors: Seboka Binyam Tariku , Hailegebreal Samuel , Yehualashet Delelegn Emwodew , Demeke Abel Desalegn
Published: June 2021

Background

Undernutrition is a major public health concern among under-five children in many developing countries. This work evaluated the overall prevalence of under-nutrition by using a composite index of anthropometric failure (CIAF), which helps in the detection of children with multiple anthropometric failures. This research also includes the Spatio-temporal distribution of childhood anthropometric failures across time.

Methods

Secondary data was obtained from the Ethiopian Demographic and Health Survey for the survey 2005, 2011, and 2016 years. Data included 23,864 samples of children between the ages of 0–59 months, which is a nationally representative sample in Ethiopia. Other than descriptive statistics, the multivariate multilevel logistic regression was used to identify associated factors, and Getis-Ord spatial statistical tools were employed to identify high and low hotspots areas of anthropometric failures.

Result

The prevalence obtained with CIAF in 2005, 2011, and 2016 was, 53.5 %, 51 %, and 46.2 % of children were suffering from under-nutrition respectively. The spatial analysis revealed areas that are at a higher risk of anthropometric failures consistently were found in northern parts of the country, largely in the Amhara, Tigray, and Afar regions. Multilevel logistic regression analysis showed that the risk of anthropometric failure was higher among older children, had low birth weight, had a mother with low BMI, was in a rural area, had mothers and fathers without formal education.

Conclusions

In addition to identifying wasted, stunted, and underweight children, CIAF also identified children with multiple conditions, which are often overlooked in nutritional surveys. As revealed by this composite index, the prevalence of anthropometric failure remains considerably high and its spatial distribution also significantly varied across the regions in the country. The established socio-demographic characteristics and districts with a higher risk of anthropometric failure can be used to develop localized intervention and prevention strategies to improve Ethiopian children’s nutritional status and healthcare.
Monocular central retinal artery occlusion caused by bilateral internal carotid artery hypoplasia complicated with patent foramen ovale: a case report and review of literature
Authors: Zhu Lanbing , Xu Na , Li Yan
Published: June 2021

Background

Central retinal artery occlusion (CRAO) is an emergent ophthalmic disease which is commonly caused by atherosclerosis, thromboembolism, and arteriospasm. Here, we report a case of CRAO which is caused by extreme rare bilateral internal carotid artery (ICA) hypoplasia complicated with patent foramen ovale (PFO). The cardiogenic emboli blocked central retinal artery through unclosed foramen ovale and specific blood flow pathway.

Case presentation

This report describes a case of a 46-year-old woman sudden onset with amaurosis fugax for about 20 min and persistent visual impairment of left eye. Fundus fluorescein angiography shows the arm-retinal circulation time of left eye is 25 s, indicating that the occlusion occurs in the pathway from aortic arch to ophthalmic artery. The MRA and CTA examinations reveal the bilateral ICA hypoplasia and variation of Wills circle. Furthermore, transesophageal echocardiography (TEE) confirms the PFO and cardiogenic embolic event.

Conclusions

This work presents a CRAO case caused by rare congenital hypoplasia of ICA complicated with PFO, reminding us every single cause of vascular disease should be investigated carefully and the TOAST typing of cerebrovascular disease can be of great reference to the ocular vascular disease.
Public debt dynamics: the interaction with national income and fiscal policy
Authors: Spyrakis Vasileios , Kotsios Stelios
Published: June 2021

The 2008 financial crisis triggered the debt crisis in Europe. High debt-to-GDP ratios made it impossible for some countries to apply countercyclical policy in order to overcome the recession. As a result, highly indebted countries were forced to apply austerity measures to avoid sovereign default, which deepened even further the decline of their GDP. We examine the case of a highly indebted country, which is not cut off from the financial markets yet, using a bilinear difference equation system. We contemplate the dynamic equations of national income and sovereign debt together, as GDP fluctuations directly affect the debt evolution and we introduce the notion of the second relation, namely the deceleration of private investments due to sovereign debt. We build a new method for the implementation of fiscal policy, a feedback control of the economic system, and we stress its consequent policy implications. We contribute to the existing debt dynamics literature providing a new perspective for the interaction of public debt and GDP. The fiscal policy method we propose vanishes the dilemma between the front-loaded and back-loaded austerity, combines the fiscal recovery from a recession and the fiscal consolidation, as it immediately improves the debt-to-GDP ratio by increasing the national income and restraining the rise of public debt. Finally, we stress why the second relation is important for the implementation of fiscal policy, as its presence leads to a slower and more painful recovery.
Dietary resveratrol attenuation of intestinal inflammation and oxidative damage is linked to the alteration of gut microbiota and butyrate in piglets challenged with deoxynivalenol
Authors: Qiu Yueqin , Yang Jun , Wang Li , Yang Xuefen , Gao Kaiguo , Zhu Cui , Jiang Zongyong
Published: June 2021

Background

Deoxynivalenol (DON) is a widespread mycotoxin that induces intestinal inflammation and oxidative stress in humans and animals. Resveratrol (RES) effectively exerts anti-inflammatory and antioxidant effects. However, the protective effects of RES on alleviating DON toxicity in piglets and the underlying mechanism remain unclear. Therefore, this study aimed to investigate the effect of RES on growth performance, gut health and the gut microbiota in DON-challenged piglets. A total of 64 weaned piglets [Duroc × (Landrace × Yorkshire), 21-d-old, 6.97 ± 0.10 kg body weight (BW)] were randomly allocated to 4 treatment groups (8 replicate pens per treatment, each pen containing 2 males; n = 16 per treatment) for 28 d. The piglets were fed a control diet (CON) or the CON diet supplemented with 300 mg RES/kg diet (RES group), 3.8 mg DON/kg diet (DON) or both (DON+RES) in a 2 × 2 factorial design.

Results

DON-challenged piglets fed the RES-supplemented diet had significantly decreased D-lactate concentrations and tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) mRNA and protein expression, and increased zonula occludens-1 (ZO-1) mRNA and protein expression compared with those of DON-challenged piglets fed the unsupplemented diet (P < 0.05). Compared with unsupplemented DON-challenged piglets, infected piglets fed a diet with RES showed significantly decreased malondialdehyde (MDA) levelsand increased mRNA expression of antioxidant enzymes and antioxidant genes (i.e., GCLC, GCLM, HO-1, SOD1 and NQO-1) and glutamate-cysteine-ligase modulatory subunit (GCLM) protein expression (P < 0.05). Moreover, RES supplementation significantly abrogated the increase in the proportion of TUNEL-positive cells and the protein expression of caspase3 in DON-challenged piglets (P < 0.05). Finally, RES supplementation significantly increased the abundance of Roseburia and butyrate concentrations, while decreasing the abundances of Bacteroides and unidentified-Enterobacteriaceae in DON-challenged piglets compared with DON-challenged piglets alone (P < 0.05).

Conclusions

RES supplementation improved gut health in DON-challenged piglets by strengthening intestinal barrier function, alleviating intestinal inflammation and oxidative damage, and positively modulating the gut microbiota. The protective effects of RES on gut health may be linked to increased Roseburia and butyrate concentrations, and decreased levels of Bacteroides and unidentified-Enterobacteriaceae.
Spatial–temporal pattern of cutaneous leishmaniasis in Brazil
Authors: Portella Tatiana P. , Kraenkel Roberto A.
Published: June 2021

Background

Cutaneous leishmaniasis (CL) is a vector-borne disease classified by the World Health Organization as one of the most neglected tropical diseases. Brazil has the highest incidence of CL in America and is one of the ten countries in the world with the highest number of cases. Understanding the spatiotemporal dynamics of CL is essential to provide guidelines for public health policies in Brazil. In the present study we used a spatial and temporal statistical approach to evaluate the dynamics of CL in Brazil.

Methods

We used data of cutaneous leishmaniasis cases provided by the Ministry of Health of Brazil from 2001 to 2017. We calculated incidence rates and used the Mann–Kendall trend test to evaluate the temporal trend of CL in each municipality. In addition, we used Kuldorff scan method to identify spatiotemporal clusters and emerging hotspots test to evaluate hotspot areas and their temporal trends.

Results

We found a general decrease in the number of CL cases in Brazil (from 15.3 to 8.4 cases per 100 000 habitants), although 3.2% of municipalities still have an increasing tendency of CL incidence and 72.5% showed no tendency at all. The scan analysis identified a primary cluster in northern and central regions and 21 secondary clusters located mainly in south and southeast regions. The emerging hotspots analysis detected a high spatial and temporal variability of hotspots inside the main cluster area, diminishing hotspots in eastern Amazon and permanent, emerging, and new hotspots in the states of Amapá and parts of Pará, Roraima, Acre and Mato Grosso. The central coast the state of Bahia is one of the most critical areas due to the detection of a cluster of the highest rank in a secondary cluster, and because it is the only area identified as an intensifying hotspot.

Conclusions

Using a combination of statistical methods we were able to detect areas of higher incidence of CL and understand how it changed over time. We suggest that these areas, especially those identified as permanent, new, emerging and intensifying hotspots, should be targeted for future research, surveillance, and implementation of vector control measures.

Graphic abstract
Transformative eating disorder research: qualitative research considerations
Authors: Janse van Rensburg Margaret G.
Published: June 2021

This letter identifies the potential of qualitative eating disorder research to work within a transformative paradigm that naturalizes the state of living with an eating disorder. The number of qualitative research publications with persons living with eating disorders have increased, however, a substantive proportion of this qualitative research follows traditional research paradigms that are built upon the assumption that eating disorders signify a personal deficit. Transformative qualitative eating disorder research has potential to include those living with eating disorders in all stages of the research process to ensure that research leads to the de-stigmatization of eating disorders promoting health, wellbeing, and quality of life for persons living with eating disorders.
Autophagy is affected in patients with hypokalemic periodic paralysis: an involvement in vacuolar myopathy?
Authors: Krag Thomas O. , Holm-Yildiz Sonja , Witting Nanna , Vissing John
Published: June 2021

Hypokalemic periodic paralysis is an autosomal dominant, rare disorder caused by variants in the genes for voltage-gated calcium channel CaV1.1 (CACNA1S) and NaV1.4 (SCN4A). Patients with hypokalemic periodic paralysis may suffer from periodic paralysis alone, periodic paralysis co-existing with permanent weakness or permanent weakness alone. Hypokalemic periodic paralysis has been known to be associated with vacuolar myopathy for decades, and that vacuoles are a universal feature regardless of phenotype. Hence, we wanted to investigate the nature and cause of the vacuoles. Fourteen patients with the p.R528H variation in the CACNA1S gene was included in the study. Histology, immunohistochemistry and transmission electron microscopy was used to assess general histopathology, ultrastructure and pattern of expression of proteins related to muscle fibres and autophagy. Western blotting and real-time PCR was used to determine the expression levels of proteins and mRNA of the proteins investigated in immunohistochemistry. Histology and transmission electron microscopy revealed heterogenous vacuoles containing glycogen, fibrils and autophagosomes. Immunohistochemistry demonstrated autophagosomes and endosomes arrested at the pre-lysosome fusion stage. Expression analysis showed a significant decrease in levels of proteins an mRNA involved in autophagy in patients, suggesting a systemic effect. However, activation level of the master regulator of autophagy gene transcription, TFEB, did not differ between patients and controls, suggesting competing control over autophagy gene transcription by nutritional status and calcium concentration, both controlling TFEB activity. The findings suggest that patients with hypokalemic periodic paralysis have disrupted autophagic processing that contribute to the vacuoles seen in these patients.
Exploration of spatial distribution of brain metastasis from small cell lung cancer and identification of metastatic risk level of brain regions: a multicenter, retrospective study
Authors: Wang Yong , Xia Wei , Liu Baoyan , Zhou Liu , Ni Meng , Zhang Rui , Shen Jingyi , Bai Yujun , Weng Guixiang , Yuan Shuanghu , Gao Xin
Published: June 2021

Objectives

This study aimed to explore the spatial distribution of brain metastases (BMs) from small cell lung cancer (SCLC) a homogenous sample, and to identify the metastatic risk levels in brain regions.

Methods

T1-enhanced magnetic resonance imaging (MRI) from SCLC patients were retrospectively reviewed from three medical institutions in China. All images were registered to the standard brain template provided by the Montreal Neurological Institute (MNI) 152 database, followed by transformation of the location of all BMs to the space of standard brain. The MNI structural atlas and Anatomical Automatic Labeling (AAL) atlas were then used to identify the anatomical brain regions, and the observed and expected rates of BMs were compared using 2-tailed proportional hypothesis testing. The locations and sizes of brain lesions were analyzed after image standardization.

Results

A total of 215 eligible patients with 1033 lesions were screened by MRI, including 157 (73%) males and 58 (27%) females. The incidence of crucial structures were as follows: hippocampus 0.68%, parahippocampal 0.97%, brainstem 2.05%, cauate 0.68%, putamen 0.68%, pallidum 0.2%, thalamus 1.36%. No BMs were found in the amygdala, pituitary gland, or pineal gland. The cumulative frequency of the important structures was 6.62%. Based on the results of MNI structural atlas, the cerebellum, deep white matter and brainstem was identified as a higher risk region than expected for BMs (P = 9.80 ×10−15, 9.04 ×10−6), whereas temporal lobe were low-risk regions (P = 1.65 ×10−4). More detailed AAL atlas revealed that the low-risk regions for BMs was inferior frontal gyrus (P = 6.971 ×10−4), while the high-risk regions for BMs was cerebellar hemispheres (P = 1.177 ×10−9).

Conclusion

Many crucial structures including the hippocampus, parahippocampus, pituitary gland and thalamus etc. have low frequency of brain metastases in a population of SCLC patients. This study provides the help to investigate the clinical feasibility of HA-WBRT and non-uniform dose of PCI in a population of SCLC patients.
Surgical management of post-surgical intercostal thoracic-abdominal nerve neuroma
Authors: Raikar Soubrata , Patil Arun Angelo , Simmons Amelia , Nilles-Melchert Thomas
Published: June 2021

Background

Formation of post-operative neuroma formation after laparoscopic surgery is not common. Its diagnosis is often missed because pain often mimics intra-abdominal pathology. In this paper, the authors report a case in which the severe pain resulting from the abovementioned neuroma was successfully treated by excision of neuroma and implant of the proximal stump into the adjacent muscle.

Case presentation

The patient is a 20-year-old female who had laparoscopic surgery on her left kidney. Immediately after surgery, she started experiencing severe pain at the operative site that continued for 5 years. A recent nerve block of the thoracic-abdominal intercostal nerve deep in the abdominal wall immediately beneath the incision gave her temporary relief for a couple of weeks. The patient was operated on. The neuroma was identified in the scar tissue of the transversalis muscle. The neuroma was excised, and the proximal stump was buried in the adjacent muscle. After the operation, she was free of pain and continues to be free of pain at 6 months follow-up.

Conclusion

Formation of neuroma with severe chronic abdominal pain can occur after laparoscopic surgery. Nerve block is a diagnostic study for this condition. Neuroma resection with burying the covering of the stump can result in the cure of the pain.
A cloud-based service-oriented architecture to unlock smart energy services
Authors: Haghgoo Maliheh , Dognini Alberto , Storek Thomas , Plamanescu Radu , Rahe Ulrike , Gheorghe Stefan , Albu Mihaela , Monti Antonello , Müller Dirk
Published: June 2021

In a modern smart energy system with increased penetration of renewable energy resources, the amount of data from various sources is growing significantly. Such systems require complex algorithms and controlling on-demand. These requirements can be addressed with on-demand scalability and a stable system. Nowadays, on-demand scalability is achieved by considering cloud computing and Internet of Things (IoT) technologies. This paper presents a cloud-based platform based on service-oriented architecture to perform analyzes on smart energy system services. It is the result of the European FISMEP (FIWARE for Smart Energy Platform) project to demonstrate an information and communication technology (ICT) architecture for the smart energy sector. The presented architecture is powered by FIWARE, open-source and customizable building blocks for future internet applications and services. Furthermore, the feasibility of the architecture is evaluated using various test cases.
Molecular basis of pathogenesis of postharvest pathogenic Fungi and control strategy in fruits: progress and prospect
Authors: Zhang Zhan-Quan , Chen Tong , Li Bo-Qiang , Qin Guo-Zheng , Tian Shi-Ping
Published: June 2021

The disease caused by pathogenic fungi is the main cause of postharvest loss of fresh fruits. The formulation of disease control strategies greatly depends on the understanding of pathogenic mechanism of fungal pathogens and control strategy. In recent years, based on the application of various combinatorial research methods, some pathogenic genes of important postharvest fungal pathogens in fruit have been revealed, and their functions and molecular regulatory networks of virulence have been explored. These progresses not only provide a new perspective for understanding the molecular basis and regulation mechanism of pathogenicity of postharvest pathogenic fungi, but also are beneficial to giving theoretical guidance for the creation of new technologies of postharvest disease control. Here, we synthesized these recent advances and illustrated conceptual frameworks, and identified several issues on the focus of future studies.
Introduction
Authors: Celikates Robin
Published: June 2021

Violence manifests as a force that dissects: it disjoins, divides, breaks up lives and bodies, communities, the environment. It also constitutes a field of forces that theory, in its critical registers, is trying to dissect, to anatomize, to take apart, to lay open, to open up for critique and transformation, especially when violence takes hidden, invisibilized, or structural forms. As Étienne Balibar's work exemplifies, for theory to do this, it not only needs to take account of the resistance and struggles of its age; it also needs to move beyond clichés about violence as the intentional infliction of bodily harm, and beyond the widespread assumption that violence is the absolute other of politics, that politics and violence are incompatible. The commentaries in this special section further explore the theoretical space opened up by Balibar's work in light of the current conjuncture.
Introduction
Authors: Zambrana Rocío
Published: June 2021

The essays translated in this cluster explore the work of debt, blame, and responsibility in the continuation of and resistance to colonial life in contemporary Puerto Rico. In the colony of Puerto Rico, debt represents the continuation of the colonial condition—Puerto Rico's status as an unincorporated territory of the United States. Ariadna Michelle Godreau-Aubert, Vanesa Contreras Capó, Anayra Santory Jorge, and Eva Prados Rodríguez show furthermore how debt actualizes a racial and gender order that exceeds colonialism as a juridical-political predicament. Their essays track forms of resistance to the work of debt.
Pósters · “Création – créativité: entre formation et recherche”.
Authors: Deguines Guillem Clara , Vives Almansa Rosa , Rosello Matilde
Published: June 2021

Los pósters que se publican en este volumen fueron presentados en el coloquio internacional “Création – créativité: entre formation et recherche”, París, 2017: Proyecto Olma et Ofe. Libros ilustrados/vs/Ejercicios de coloriage dentro de la educación artística, de Clara Deguines Guillem, La cabaña para crear, de Rosa Vives Almansa y Museos vivos, museos inclusivos, de Matilde Rosello.
Negative pressure wound therapy—two novel approaches to healing dehisced vascular bypass wounds
Authors: O'Malley Paula , McDonnell Ciaran
Published: June 2021

The use of negative pressure wound therapy (NPWT) in surgical wound healing by secondary intention is well known. Its use in healing dehisced vascular bypass wounds is contraindicated by manufacturers due to exposed vasculature and risk of bleeding. There is an increasing body of knowledge to support the use of NPWT in vascular wounds in order to prevent graft excision and the need for flap closure. This paper reports the use of two different approaches using NPWT to heal dehisced, infected vascular groin bypass wounds in two patients. Both patients had lower limb bypass using Dacron (Vascutek Ltd., UK) grafts and subsequently became infected, dehisced and required debridement. Following debridement, graft was visible in the wound bed and NPWT was applied to facilitate healing. Case one had polyurethane (black) foam and a layer of petroleum-impregnated cellulose acetate mesh to prevent adherence to the graft. Case two had polyvinyl alcohol (white) (PVA) foam applied to the wound. The PVA foam was used in Case two due to pain at dressing changes. Negative pressure was initially –25mmHg but increased gradually to –125mmHg and –150mmHg, respectively, the therapeutic pressure for the respective foams. Dressings were changed every 48–72 hours and infection treated with antibiotics as appropriate. After eight days and 28 days of NPWT, respectively, graft was no longer visible. No significant bleeding was noted. These two case studies would suggest that, with precautions taken to protect the vasculature, the use of NPWT in healing dehisced vascular groin wounds is an appropriate treatment.
Fatal necrotising cutaneous mucormycosis due to novel Saksenaea species: a case study
Authors: Kachuei Reza , Badali Hamid , Vaezi Afsane , Jafari Nematollah Jonaidi , Ahmadikia Kazem , Kord Mohammad , Aala Farzad , Al-Hatmi Abdullah MS , Khodavaisy Sadegh
Published: June 2021

This case report describes the progressive wound infection in the left thigh of a 34-year-old man due to an old landmine explosion. The infection developed into rapidly spreading skin and soft tissue necrotising Saksenaea infection, despite antifungal therapy and surgical debridement. The report provides evidence that Saksenaea spp. should be added to the list of mucoralean fungi that can cause severe necrotising infection. It also highlights the need for improved early diagnostic procedures and enhanced understanding of Saksenaea virulence factors that contribute to necrotising infection.
What is the role of incisional vacuum therapy in challenging spinal wounds? A single centre experience
Authors: Hajjar Marwan S , Atallah Georgio M , Oneissi Ahmad , Beaineh Paul , Abu-Sittah Ghassan S
Published: June 2021

Objective:

A surgical approach to the treatment of spinal defects and disorders has become more common because of the medical and technological advancements achieved in the last decade. This rising trend in spinal surgeries is associated with adverse events, most notably wound complications. From its introduction, negative pressure wound therapy (NPWT) has proved to be essential in the management of complex wounds and in speeding up wound recovery. The aim of this study is to investigate the use of incisional NPWT in patients undergoing spinal surgery and its role in the prevention of wound complications.

Method:

This study is a retrospective medical chart review conducted on patients who underwent spinal surgery and received incisional vacuum therapy as part of their treatment. The apparatus was applied intraoperatively following the spinal surgery for all patients included in this study. All surgical procedures were conducted between September 2019 and May 2020. Data entry and analysis were performed between September and October 2020.

Results:

A total of five patients' records were reviewed. In our healthcare centre, three patients developed seroma, one developed haematoma, four required revision surgery and one patient required re-operation. There was no wound dehiscence and none of the wounds became infected. Mean length of hospital stay was 11.2 days (standard deviation (SD): 9.5 days) and mean operation time was 333 minutes (SD: 86.4 minutes).

Conclusion:

There is a scarcity of data on the role of incisional vacuum therapy in the prevention of wound complications associated with spine surgeries. Our study showed promising results for the use of incisional NPWT in the management of spinal wounds. Further research is required in order to enhance wound care by exploiting this potentially beneficial approach.