bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

AbstractThe 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

Abstract
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

Abstract
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

AbstractThe 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

Abstract
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

Abstract
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

AbstractThis 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

AbstractHypokalemic 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.