bluuebunny/crossref_metadata_2025 huggingface dataset:
Small-molecule Akt-activation in airway cells induces NO production and reduces IL-8 transcription through Nrf-2
Authors: Gopallawa Indiwari , Kuek Li Eon , Adappa Nithin D. , Palmer James N. , Lee Robert J.
Published: October 2021

Background

The non-cancerous functions of Akt in the airway are understudied. In some tissues, Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) to produce nitric oxide (NO) that has anti-inflammatory effects. NO production has antibacterial and antiviral effects in the airway, and increasing NO may be a useful anti-pathogen strategy. Akt also stimulates the nuclear factor erythroid 2–related factor 2 (Nrf-2) transcription factor, which transcribes antioxidant genes. Therefore, we hypothesized that activation of the Akt/eNOS pathway, which also activates Nrf-2, may have protective effects in human airway cells against injury.

Methods

To directly test the effects of Akt signaling in the airway, we treated A549 and 16HBE cells as well as primary bronchial, nasal, and type II alveolar epithelial cells with small molecule Akt activator SC79. We examined the effects of SC79 on eNOS activation, NO production, Nrf-2 target levels, and interleukin-8 (IL-8) transcription during exposure to TNF-α or Pseudomonas flagellin (TLR5 agonist). Additionally, air–liquid interface bronchial cultures were treated with cadmium, an oxidative stressor that causes airway barrier breakdown.

Results

SC79 induced a ~ twofold induction of p-eNOS and Nrf-2 protein levels blocked by PI3K inhibitor LY294002. Live cell imaging revealed SC79 increased acute NO production. Quantitative RT-PCR showed a ~ twofold increase in Nrf-2 target gene transcription. TNF-α or flagellin-induced IL-8 levels were also significantly reduced with SC79 treatment. Moreover, the transepithelial electrical resistance decrease observed with cadmium was ameliorated by SC79, likely by an acute increase in tight junction protein ZO-1 levels.

Conclusions

Together, the data presented here demonstrate SC79 activation of Akt induces potentially anti-pathogenic NO production, antioxidant gene transcription, reduces IL-8 transcription, and may protect against oxidative barrier dysfunction in a wide range of airway epithelial cells.
The impact of mosquito proof lids of underground tanks “tanka” on the breeding of Anopheles stephensi in a village in western Rajasthan, India
Authors: Singh Himmat , Gupta Sanjeev Kumar , Vikram Kumar , Saxena Rekha , Sharma Amit
Published: October 2021

Background

Western Rajasthan in India has a typical desert climate. Until the introduction of the canal water irrigation system, malaria was an unstable and seasonal occurrence. Due to the scarcity of water, the community practised having one large underground tank (locally known as the tanka) in their house to collect rainwater for long-term household use. Anopheles stephensi, one of the major malaria vectors, breeds in improperly covered "tankas” if not properly covered and harbours a vector population throughout the year.

Methods

Two villages, Ajasar (intervention) and Tota (control), with similar ecological features, were selected for the study. A pre-intervention survey was carried out in both villages to assess the presence and quality of lids of tankas, and mosquito breeding and adult mosquito density. Awareness of the community about malaria and mosquitoes was also assessed during the pre-intervention period. In the intervention village, damaged or improper lids were replaced with improved mosquito proof polyvinyl chloride plastic (PVC) lids and lasted longer than the conventional lids. The fitness of the lids was assessed one year after the pre-intervention survey. The entomological assessment was carried out in both intervention and non-intervention villages. The level of community awareness about malaria, mosquitoes, their breeding places, and the role of tankas in malaria transmission was assessed both during pre- and post-intervention.

Results

During the pre-intervention survey,Anopheles breeding was found in 22.1% (58/262) of tankas in the intervention village and 27.1% (19/70) in tankas in the control village. Mosquito breeding was observed in the tankas with iron lids in the intervention village (48.3%) and the control village (42.1%). In the intervention village, out of 262 tankas in the village, 200 lids were replaced, resulting in the complete absence of mosquito breeding.

In the pre-intervention survey conducted in May 2018, Anopheles stephensi consisted of 46% of adult mosquitoes in the intervention village and 55% in the control village. Its density was significantly reduced to 0.55 per man-hour (94.95%) and 0.22 per man-hour (97.8%) in the post-intervention survey in June 2018 and a follow-up survey in May 2019, respectively, in the intervention village.

Discussion

The density of Anopheles stephensi adults was reduced significantly (97.8%) in the intervention village due to complete prevention of breeding in the underground tankas in the intervention village as compared to the control with no density reduction. The awareness level of the community was also improved due to their involvement in the study.

Conclusion

Provision of proper metal lids or replacement of damaged lids on underground water storage tanks as an environmental management approach prevented the breeding of  the malaria vector, Anopheles stephensi, in a desert village in western Rajasthan.
An equity and efficiency integrated grid-to-level 2SFCA approach: spatial accessibility of multilevel healthcare
Authors: Zhang Shaoyao , Song Xueqian , Zhou Jie
Published: October 2021

Background

Equity of healthcare spatial access is essential for the health outcomes of medical investments and the welfare of populations, and efficiency of medical resource allocation is important for obtaining a supply-demand equilibrium with lower cost and higher outputs with limited inputs. However, the literature that involves both equity and efficiency in its analysis of healthcare spatial allocation is rare, and the spatial accessibility of multilevel healthcare is difficult to measure by traditional methods in a large region with diversified population distribution.

Methods

To assist in solving these issues, this paper aims to build an equity and efficiency integrated analytical framework by proposing a new “GTL-2SFCA” approach to analyze the spatial accessibility of multilevel healthcare; maximum and minimum floating catchments of different levels of healthcare were assigned to ensure a combination of universal search coverage and efficient hospitalization behavior simulation.

Results

The analytical framework was applied and tested in Hubei, China. Almost half of the residents (47.95%) and townships (44.98%) have access to both public general hospitals (PGHs) and primary healthcare centers (PHCs) services, 36.89% of the residents enjoy only one sufficient service, either PGHs or PHCs, and the remaining residents (15.16%) are faced with the risk of lacking access to both services. The results reveal that there are core-periphery effects of multilevel healthcare throughout Hubei and isolate clusters that have adequate access in the western region. The polarization effect of higher-level healthcare and the polycentric pattern of lower-level healthcare coexist. The multilevel healthcare shortage was identified in some areas in boundary and peripheral regions.

Conclusions

This study integrates equity and efficiency into the GTL-2SFCA framework, enriches the FCA series methodologies and provides a more operational solution for evaluating the access of residents in more sophisticated spatial units to each level of healthcare. By more significantly differing and quantifying the catchment area and distance decay effect, this methodology avoids overestimating or underestimating accessibility and discovers some imperceptible spatial inequities. This study has application value for researchers and decision-makers in other scenarios and regions with significant heterogeneity in medical resources and where the population has greater mobility.
A novel dual-prodrug carried by cyclodextrin inclusion complex for the targeting treatment of colon cancer
Authors: Chen Lin , Lin Yan , Zhang Zijun , Yang Ruisheng , Bai Xiaosheng , Liu Zhongbing , Luo Zhongling , Zhou Meiling , Zhong Zhirong
Published: October 2021

Background

There is an obvious correlation between ulcerative colitis and colorectal cancer, and the risk of colorectal cancer in patients with ulcerative colitis is increasing. Therefore, the combination therapy of anti-inflammatory and anti-tumor drugs may show promising to inhibit colon cancer. 5-aminosalicylic acid (5-ASA) with anti-inflammatory function is effective for maintaining remission in patients with ulcerative colitis and may also reduce colorectal cancer risk. Histone deacetylase (HDAC) plays an essential role in the progression of colon cancer. Butyric acid (BA) is a kind of HDAC inhibitor and thus shows tumor suppression to colon cancer. However, the volatile and corrosive nature of BA presents challenges in practical application. In addition, its clinical application is limited due to its non-targeting ability and low bioavailability. We aimed to synthesize a novel dual-prodrug of 5-ASA and BA, referred as BBA, to synergistically inhibit colon cancer. Further, based on the fact that folate receptor (FR) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in colon cancer, we took folate as the targeting ligand and used carboxymethyl-β-cyclodextrin (CM-β-CD) to carry BBA and thus prepared a novel inclusion complex of BBA/FA-PEG-CM-β-CD.

Results

It was found that BBA/FA-PEG-CM-β-CD showed significant inhibition in cell proliferation against colon cancer cells SW620. It showed a pro-longed in vivo circulation and mainly accumulated in tumor tissue. More importantly, BBA/FA-PEG-CM-β-CD gave great tumor suppression effect against nude mice bearing SW620 xenografts.

Conclusions

Therefore, BBA/FA-PEG-CM-β-CD may have clinical potential in colon cancer therapy.

Graphical Abstract
A case-control study on factor V Leiden: an independent, gender-dependent risk factor for venous thromboembolism
Authors: Takhviji Vahideh , Zibara Kazem , Maleki Asma , Azizi Ebrahim , Hommayoun Sanaz , Tabatabaei Mohammadreza , Ahmadi Seyed Esmaeil , Soleymani Maral , Ghalesardi Omid Kiani , Farokhian Mina , Davari Afshin , Paridar Pouria , Kalantari Anahita , Khosravi Abbas
Published: October 2021

Background

Activated protein C resistance (APCR) due to factor V Leiden (FVL) mutation (R506Q) is a major risk factor in patients with venous thromboembolism (VTE). The present study investigated the clinical manifestations and the risk of venous thromboembolism regarding multiple clinical, laboratory, and demographic properties in FVL patients.

Material and methods

A retrospective cross-sectional analysis was conducted on a total of 288 FVL patients with VTE according to APCR. In addition, 288 VET control samples, without FVL mutation, were also randomly selected. Demographic information, clinical manifestations, family and treatment history were recorded, and specific tests including t-test, chi-square and uni- and multi-variable regression tests applied.

Results

APCR was found to be 2.3 times significantly more likely in men (OR: 2.1, p < 0.05) than women. The risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in APCR patients was 4.5 and 3.2 times more than the control group, respectively (p < 0.05). However, APCR could not be an independent risk factor for arterial thrombosis (AT) and pregnancy complications. Moreover, patients were evaluated for thrombophilia panel tests and showed significantly lower protein C and S than the control group and patients without DVT (p < 0.0001).

Conclusion

FVL mutation and APCR abnormality are noticeable risk factors for VTE. Screening strategies for FVL mutation in patients undergoing surgery, oral contraceptive medication, and pregnancy cannot be recommended, but a phenotypic test for activated protein C resistance should be endorsed in patients with VTE.
Inhibition of lysophosphatidic acid receptor 1–3 deteriorates experimental autoimmune encephalomyelitis by inducing oxidative stress
Authors: Choi Jong Hee , Oh Jinhee , Lee Min Jung , Bae Hyunsu , Ko Seong-Gyu , Nah Seung-Yeol , Cho Ik-Hyun
Published: October 2021

Background

Lysophosphatidic acid receptors (LPARs) are G-protein-coupled receptors involved in many physiological functions in the central nervous system. However, the role of the LPARs in multiple sclerosis (MS) has not been clearly defined yet.

Methods

Here, we investigated the roles of LPARs in myelin oligodendrocyte glycoprotein peptides-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS.

Results

Pre-inhibition with LPAR1–3 antagonist Ki16425 deteriorated motor disability of EAElow. Specifically, LPAR1–3 antagonist (intraperitoneal) deteriorated symptoms of EAElow associated with increased demyelination, chemokine expression, cellular infiltration, and immune cell activation (microglia and macrophage) in spinal cords of mice compared to the sham group. This LPAR1–3 antagonist also increased the infiltration of CD4+/IFN-γ+ (Th1) and CD4+/IL-17+ (Th17) cells into spinal cords of EAElow mice along with upregulated mRNA expression of IFN-γ and IL-17 and impaired blood–brain barrier (BBB) in the spinal cord. The underlying mechanism for negative effects of LPAR1–3 antagonist was associated with the overproduction of reactive oxygen species (ROS)-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) 2 and NOX3. Interestingly, LPAR1/2 agonist 1-oleoyl-LPA (LPA 18:1) (intraperitoneal) ameliorated symptoms of EAEhigh and improved representative pathological features of spinal cords of EAEhigh mice.

Conclusions

Our findings strongly suggest that some agents that can
stimulate LPARs might have potential therapeutic implications for autoimmune demyelinating diseases such as MS.
Long-term remission of AIDS-related primary central nervous system lymphoma in a patient under antiretroviral therapy: a case report and review of the literature
Authors: Gijs Pieter-Jan , Clerc Olivier
Published: October 2021

Background

AIDS-related primary central nervous system lymphoma (AR-PCNSL) is an AIDS-defining disease that usually occurs when the CD4 count is less than 50 cells/μl. The frequency of the disease has substantially decreased in the era of highly active antiretroviral therapy (HAART). Prognosis is poor with rapid progression leading to death within 2–3 months if left untreated.

Case description

A 65 years old male presented to medical attention with gait disturbance, weight loss and slight left-sided hemiparesis. Human immunodeficiency virus infection was diagnosed with an initial CD4 count of 116 cells/µl and a viral load of 260,000 copies/ml. Magnetic resonance imaging of the brain revealed three brain lesions involving the right frontal lobe and the left parietal lobe, which on biopsy led to a diagnosis of AR-PCNSL. HAART was initiated with whole-brain radiotherapy (WBRT), and the patient declined systemic chemotherapy. Due to poor performance status, he was transferred to palliative care. Under HAART, he slowly recovered with normalization of CD4 count and undetectable viral load. Medical imaging showed complete remission (CR) of the brain lesions. At 3-year follow-up, the patient remains in CR, but presented mild neurocognitive dysfunction possibly secondary to WBRT.

Conclusion

Nowadays, treatment paradigm parallels that of primary central nervous system lymphoma in the immunocompetent population based on systemic chemotherapy (primarily high-dose intravenous methotrexate and steroids) in association with HAART. The role of WBRT is questionable because of late neurotoxic effects.
Adjunctive cytoprotective therapies in acute ischemic stroke: a systematic review
Authors: Mulder I. A. , van Bavel E. T. , de Vries H. E. , Coutinho J. M.
Published: October 2021

With the introduction of endovascular thrombectomy (EVT), a new era for treatment of acute ischemic stroke (AIS) has arrived. However, despite the much larger recanalization rate as compared to thrombolysis alone, final outcome remains far from ideal. This raises the question if some of the previously tested neuroprotective drugs warrant re-evaluation, since these compounds were all tested in studies where large-vessel recanalization was rarely achieved in the acute phase. This review provides an overview of compounds tested in clinical AIS trials and gives insight into which of these drugs warrant a re-evaluation as an add-on therapy for AIS in the era of EVT. A literature search was performed using the search terms “ischemic stroke brain” in title/abstract, and additional filters. After exclusion of papers using pre-defined selection criteria, a total of 89 trials were eligible for review which reported on 56 unique compounds. Trial compounds were divided into 6 categories based on their perceived mode of action: systemic haemodynamics, excitotoxicity, neuro-inflammation, blood–brain barrier and vasogenic edema, oxidative and nitrosative stress, neurogenesis/-regeneration and -recovery. Main trial outcomes and safety issues are summarized and promising compounds for re-evaluation are highlighted. Looking at group effect, drugs intervening with oxidative and nitrosative stress and neurogenesis/-regeneration and -recovery appear to have a favourable safety profile and show the most promising results regarding efficacy. Finally, possible theories behind individual and group effects are discussed and recommendation for promising treatment strategies are described.
Effects of foreign direct investment and trade on the prevalence of tobacco consumption in Africa: a panel study
Authors: Immurana Mustapha , Boachie Micheal Kofi , Kisseih Kwame Godsway
Published: October 2021

Background

As African governments take measures to enhance international trade and Foreign Direct Investment (FDI) inflows, a major concern is that, these measures can make Africa more vulnerable to the strategies of the tobacco industry. This concern is based on the fact that, each year, tobacco use is estimated to be responsible for the deaths of over eight million people in the world. However, there is very little empirical evidence to refute or confirm the above concern, especially in the African context. This study therefore investigates the effects of FDI and trade on the prevalence of tobacco consumption in Africa.

Methods

Data on a sample of 31 African countries for the period, 2010–2018 are used. The system Generalised Method of Moments (GMM) regression model is employed as the empirical estimation technique.

Results

The findings show that, FDI and trade have negative and positive significant association with the prevalence of tobacco consumption respectively. These findings are robust even after using different specifications and indicators of FDI and trade.

Conclusion

Rising trade (and not FDI) should be of concern to African governments in the quest to reduce the prevalence of tobacco consumption on the continent.
Wheat physiology predictor: predicting physiological traits in wheat from hyperspectral reflectance measurements using deep learning
Authors: Furbank Robert T. , Silva-Perez Viridiana , Evans John R. , Condon Anthony G. , Estavillo Gonzalo M. , He Wennan , Newman Saul , Poiré Richard , Hall Ashley , He Zhen
Published: October 2021

Background

The need for rapid in-field measurement of key traits contributing to yield over many thousands of genotypes is a major roadblock in crop breeding. Recently, leaf hyperspectral reflectance data has been used to train machine learning models using partial least squares regression (PLSR) to rapidly predict genetic variation in photosynthetic and leaf traits across wheat populations, among other species. However, the application of published PLSR spectral models is limited by a fixed spectral wavelength range as input and the requirement of separate custom-built models for each trait and wavelength range. In addition, the use of reflectance spectra from the short-wave infrared region requires expensive multiple detector spectrometers. The ability to train a model that can accommodate input from different spectral ranges would potentially make such models extensible to more affordable sensors. Here we compare the accuracy of prediction of PLSR with various deep learning approaches and an ensemble model, each trained and tested using previously published data sets.

Results

We demonstrate that the accuracy of PLSR to predict photosynthetic and related leaf traits in wheat can be improved with deep learning-based and ensemble models without overfitting. Additionally, these models can be flexibly applied across spectral ranges without significantly compromising accuracy.

Conclusion

The method reported provides an improved prediction of wheat leaf and photosynthetic traits from leaf hyperspectral reflectance and do not require a full range, high cost leaf spectrometer. We provide a web service for deploying these algorithms to predict physiological traits in wheat from a variety of spectral data sets, with important implications for wheat yield prediction and crop breeding.
Undetectable thyroglobulin makes 123I whole-body scan and stimulated thyroglobulin obsolete in follow-up care of differentiated thyroid cancer: a retrospective study
Authors: Sol Bastiaan , Bravenboer Bert , Velkeniers Brigitte , Raeymaeckers Steven , Keyaerts Marleen , Andreescu Corina Emilia
Published: October 2021

Background

Differentiated thyroid cancer (DTC) is a common malignancy with increasing incidence. Follow-up care for DTC includes thyroglobulin (Tg) measurement and ultrasound (US) of the neck, combined with 131I remnant ablation when indicated. Diagnostic precision has evolved with the introduction of the new high-sensitive Tg-assays (sensitivity ≤0.1 ng/mL). The aim of the study was to determine the prognostic utility of high-sensitive Tg and the need for other diagnostic tests in DTC.

Methods

This was a retrospective, observational study. Patients with pathologically confirmed DTC, treated with total thyroidectomy and 131I remnant ablation, who had their complete follow-up care in our institution were selected (October 2013–December 2018). Subjects with possible thyroglobulin autoantibody interference were excluded. Statistical analysis was performed using the IBM SPSS® Statistics 24 software package.

Results

Forty patients were eligible for analysis. A total of 24 out of the 40 patients (60%) had an undetectable high-sensitive Tg 6 months after total thyroidectomy. None of these patients had a stimulated Tg above 1 ng/mL, or remnant on the 123I Whole-Body Scan (WBS) after 1 year of follow-up. Ultrasound of the neck, performed between 6 and 12 months postoperative, was negative in 21 out of the 24 patients.

Conclusions

This study shows that an undetectable high-sensitive Tg can change the management of patients with DTC and decrease the use and need of stimulated Tg and 123I WBS.
Automatic barcode gap discovery reveals diverse clades of Rhipicephalus spp. and Haemaphysalis spp. ticks from small mammals in 'Asir, Saudi Arabia
Authors: Alghamdi Samia Q. , Low Van Lun , Alkathiry Hadil A. , Alagaili Abdulaziz N. , McGarry John W. , Makepeace Benjamin L.
Published: October 2021

Background

The ixodid tick genera Rhipicephalus and Haemaphysalis contain several species of medical and/or veterinary importance, but their diversity in some regions of the world remains under-explored. For instance, very few modern studies have been performed on the taxonomy of these genera on the Arabian Peninsula.

Methods

In this study, we trapped small mammals in the 'Asir Mountains of south-western Saudi Arabia and collected tick specimens for morphological examination and molecular barcoding, targeting three mitochondrial loci: cox1, 16S rRNA and 12S rRNA.

Results

We obtained a total of 733 ticks (608 Haemaphysalis spp. and 125 Rhipicephalus spp.) from 75 small mammal hosts belonging to six species. All tick specimens were immature except for nine adults recovered from a hedgehog (Paraechinus aethiopicus). Morphologically, the Rhipicephalus ticks resembled R. camicasi, but the Haemaphysalis ticks showed differences in palp morphology compared with species previously described from Saudi Arabia. Phylogenetic analysis and automatic barcode gap discovery identified a novel clade of Rhipicephalus sp. representing most of the nymphs. This was most closely related to R. leporis, R. guilhoni and R. linnaei. The adult ticks and a small proportion of nymphs clustered with R. camicasi sequences from a previous study. Finally, the Haemaphysalis nymphs formed two distinct clades that were clearly separated from all reference sequences but closest to some African species.

Conclusions

This apparent high level of tick diversity observed in a single study site of only ~ 170 km2, on a relatively small number of hosts, highlights the potential for the discovery of new tick species on the Arabian Peninsula.

Graphical Abstract
Insulin resistance and associated factors in female adolescents from two capital cities in the north and south of Brazil
Authors: Gemelli Ivanice Fernandes Barcellos , Silva Thais Rasia , Farias Edson dos Santos , Olinto Maria Teresa Anselmo , Spritzer Poli Mara
Published: October 2021

Background

It has been described that physiological changes in glucose metabolism, represented by insulin resistance (IR), are predicted during pubertal evolution, and obesity may be associated with its persistence even at the end of puberty. The aim of this study was to investigate the prevalence of IR in female adolescents with possible associated factors and evaluate the relationship of time since menarche (< 2 vs. ≥ 2 years) in the occurrence of IR in two Brazilian capital cities: Porto Velho (RO) and Porto Alegre (RS).

Methods

This is a cross-sectional school-based study, using information from the Study of Cardiovascular Risks (ERICA) database for adolescents aged 12–17 years, enrolled in public and private schools, in municipalities with more than 100,000 inhabitants in Brazil, between 2013 and 2014. The present study included 889 adolescents, 382 in Porto Velho (PVh) and 507 in Porto Alegre (PoA). The homeostasis model assessment for insulin resistance (HOMA-IR) ≥ 3.16 and fasting insulin ≥ 15 mU/L was used to determine the outcome variable of IR. Estimates of crude and adjusted prevalence ratios with confidence intervals of 95% were calculated using Poisson regression with robust variance. Sociodemographic, behavioral, reproductive and nutritional characteristics were considered as potential confounding factors in multivariable models based on a conceptual framework of IR determination.

Results

In the total sample, the prevalence of IR was 22.03% (95% CI 17.84–26.89). After adjusting the models, age 15–17 years and time since menarche ≥ 2 years were found to act as protective factors for IR; in contrast, the highest probability of IR was observed in black adolescents, with increased waist circumference (WC) and overweight/obesity (Ow/Ob). The protective effect of two or more years since menarche (post-menarche) was observed for both higher HOMA-IR and fasting insulin in PVh; in PoA, such protection was maintained only for fasting insulin ≥ 15 mU/L after adjustments in the multivariate models.

Conclusions

IR is more prevalent during the peri-menarche period, especially in younger and black adolescents, compared to their white and post-menarche counterparts. The association between Ow/Ob and high WC with the occurrence of IR was independent of age and ethnicity variables.
Autoimmune epilepsy due to N-methyl-d-aspartate receptor antibodies in a child: a case report
Authors: Wanigasinghe Jithangi , Chang Thashi
Published: October 2021

Introduction

Seizures of autoimmune etiology may occur independent of or predate syndromes of encephalitis. We report a child with “pure” autoimmune epilepsy followed up for 7 years to highlight long-term effects of this epilepsy and the importance of early initiation and appropriate escalation of immunosuppression to achieve a good long-term outcome.

Case presentation

A previously healthy 5-year-old Sri Lankan boy presented with acute, frequent, brief focal seizures of temporal-lobe semiology without clinical and investigatory findings suggestive of central nervous system infection, tumor, structural abnormality, or metabolic causes. His epilepsy showed poor response to increasing doses and combinations of antiseizure medications. Further investigations detected N-methyl-d-aspartate receptor antibodies in serum, but not cerebrospinal fluid. Treatment with intravenous methyl prednisolone and maintenance on mycophenolate resulted in a rapid reduction, with seizure freedom achieved within 5–6 weeks. He relapsed when immunotherapy and anti seizure medications were reduced after seizure freedom for 24 months. This, and subsequent relapses, showed poor response to modification of anti-seizure medications, but treatment with immunotherapy (methyl prednisolone and rituximab) achieved complete seizure freedom. At 7-years of follow-up, he remains free of seizure for over 3 years, and has average academic performance and satisfactory quality of life.

Conclusions

Autoimmune epilepsy is a recognized independent entity. Diagnostic criteria have been suggested for its early recognition and confirmation of diagnosis. Early diagnosis and initiation of immunosuppression, with prompt escalation of treatment when necessary, remains key to good patient outcome.
Experimental evaluation of protection and immunogenicity of Streptococcus suis bacterin-based vaccines formulated with different commercial adjuvants in weaned piglets
Authors: Obradovic Milan R. , Corsaut Lorelei , Dolbec Dominic , Gottschalk Marcelo , Segura Mariela
Published: October 2021

Streptococcus suis is an important swine pathogen responsible for economic losses to the swine industry worldwide. There is no effective commercial vaccine against S. suis. The use of autogenous (“bacterin”) vaccines to control S. suis outbreaks is a frequent preventive measure in the field, although scientific data on immunogenicity and reduction in mortality and morbidity are scarce. The goal of our study is to experimentally evaluate the immunogenicity and protective efficacy against homologous challenge in weaned piglets of a S. suis serotype 2 bacterin-based vaccine formulated with six different commercial adjuvants (Alhydrogel®, Emulsigen®-D, Quil-A®, Montanide™ ISA 206 VG, Montanide™ ISA 61 VG, and Montanide™ ISA 201 VG). The vaccine formulated with Montanide™ ISA 61 VG induced a significant increase in anti-S. suis antibodies, including both IgG1 and IgG2 subclasses, protected against mortality and significantly reduced morbidity and severity of clinical signs. Vaccines formulated with Montanide ISA 206 VG or Montanide ISA 201 VG also induced a significant increase in anti-S. suis antibodies and showed partial protection and reduction of clinical signs severity. Vaccines formulated with Alhydrogel®, Emulsigen®-D, or Quil-A® induced a low and IgG1-shifted antibody response and failed to protect vaccinated piglets against a homologous challenge. In conclusion, the type of adjuvant used in the vaccine formulation significantly influenced the immune response and efficacy of the vaccine against a homologous challenge.
Some analytical and numerical results for a fractional q-differential inclusion problem with double integral boundary conditions
Authors: Shabibi Mehdi , Samei Mohammad Esmael , Ghaderi Mehran , Rezapour Shahram
Published: October 2021

In this work, we study a q-differential inclusion with doubled integral boundary conditions under the Caputo derivative. To achieve the desired result, we use the endpoint property introduced by Amini-Harandi and quantum calculus. Integral boundary conditions were considered on time scale $\mathcal{T}_{t_{0}}=\{t_{0},t_{0}q,t_{0}q^{2}, \ldots\}\cup \{0\}$

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0

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0

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. To better evaluate the validity of our results, we provided an example, some graphs, and tables.
Exploring the relationship between static fishing gear, fishing effort, and benthic biodiversity: a systematic review protocol
Authors: Fennell Hannah , Sciberras Marija , Hiddink Jan Geert , Kaiser Michel J. , Gilman Eric , Donnan David , Crawford Rory
Published: October 2021

Background and objectives

The environmental effects of static gear fishing include habitat-level effects such as permanent changes to the physical environment and the structure of the benthic and epibenthic communities. Ecosystems subjected to prolonged exposure to pressure from static gear may undergo permanent changes and may never regain their prior ‘unfished’ state even if the fishing pressure is removed entirely. These long-term changes to physical structure of benthic habitats have implications for benthic biodiversity and ecosystem functioning. Despite this, the understanding of habitat and static fishing gear interactions is limited- with most studies focusing on the impact of mobile fishing gear. The rise of ecosystem-based fisheries management (EBFM), where managers and decision-makers manage target species within their environmental context while protecting essential ecosystem services and components, has led to an increased demand for ecosystem-level reference points. A systematic review could provide clarification on the short and long-term impacts of commercial static gear fishing on benthic community diversity.

Methods

This review will examine primary studies on the relationship between static fishing gear, intensity, and benthic biodiversity to answer the primary question ‘How do different types of static fishing gear affect benthic species richness and abundance?’. A structured search will be conducted in English. The search terms used to find relevant data to answer the research question were chosen specifically for this review and were generated using the R package litsearchr. Captured articles will be screened against pre-defined eligibility criteria. The internal and external validity of remaining studies will be classified using a pre-defined framework. Studies meeting validity will be used for data extraction. Data to be extracted includes data on study design, intervention, study results, habitat and geographical context. Outcome data (such as sample sizes, means and measures of variation such as confidence intervals, standard deviations, and standard errors) will also be extracted. Information on effect modifiers will also be collected where available as well as metadata on study methodologies and general article identifiers. Data will be used for both narrative and quantitative synthesis techniques.
What evidence exists on the possible effects of urban forms on terrestrial biodiversity in western cities? A systematic map protocol
Authors: Flégeau Morgane , Soubelet Hélène , Carré Sophie , Barot Sébastien , Lagurgue Xavier , Bognon Sabine , Clergeau Philippe
Published: October 2021

Background

As urban areas expand, scientists now agree that the city is an important space for biodiversity conservation. Yet, still relatively little is known about how urban forms could have a differential impact on terrestrial species and ecosystems. If some reviews have been conducted to examine the link between biodiversity and urban characteristics at an infra-city scale, none have explored the relationship between urban organization and biodiversity and tried to assess the capacity of various urban forms to maintain and possibly favour flora and fauna in the city. The resulting map will present the state of knowledge regarding possible relationships between urban forms and its features on the establishment and settlement of terrestrial and temperate biodiversity at infra-city scale in western cities.

Methods

The systematic map will follow the Collaboration for Environmental Evidence (CEE) Guidelines. We will collect the relevant peer-reviewed and grey literature in French and English language. The scientific literature will be retrieved with the use of a search string in two publication databases, one environmental and one social science database (Web Of Science Core Collection, and Cairn.info). We will also perform supplementary searches (search engines, call for literature, search for relevant reviews). All references will be screened for relevance using a three-stage process, according to a predefined set of eligibility criteria. Our study will concentrate on urban areas at the infra-city scale in cities of the temperate biogeographical zone. The subject population will include terrestrial species and ecosystems, except for archaea and bacteria. The exposure will consider all types of urban forms described by any urban descriptors or measures including heterogeneity, fragmentation, housing density, organisation of urban matrix, urban fabric) and all types of urban features (e.g. size, age of the buildings, materials, urban artefacts). All relevant outcomes will be considered (e.g. species richness, abundance, behaviour). We will provide an open-access database of the studies included in the map. Our results will also be presented narratively, together with tables and graphs summarising the key information coded from the retained articles (e.g. study characteristics, types and areas of research that has been undertaken, types of exposure, population concerned, etc.).
ESBL/pAmpC-producing Escherichia coli and Klebsiella pneumoniae carriage among veterinary healthcare workers in the Netherlands
Authors: Meijs Anouk P. , Gijsbers Esther F. , Hengeveld Paul D. , Dierikx Cindy M. , de Greeff Sabine C. , van Duijkeren Engeline
Published: October 2021

Background

Animals are a reservoir for ESBL/pAmpC-producing Escherichia coli/Klebsiella pneumoniae (ESBL-E/K). We investigated the association between occupational contact with different types of animals and the prevalence of ESBL-E/K carriage among veterinary healthcare workers, assessed molecular characteristics of ESBL-E/K, and followed-up on the ESBL-E/K carriage status of participants and their household members.

Methods

Participants completed a questionnaire about their contact with animals at work and at home, health status, travel behaviour and hygiene, and sent in a faecal sample which was tested for the presence of ESBL-E/K. Resistance genes were typed using PCR and sequencing. ESBL-E/K positive participants and their household members were followed up after 6 months. Risk factors were analysed using multivariable logistic regression methods.

Results

The prevalence of ESBL-E/K carriage was 9.8% (47/482; 95%CI 7.4–12.7). The most frequently occurring ESBL genes were blaCTX-M-15, blaCTX-M-14 and blaDHA-1. The predominant sequence type was ST131. None of the occupation related factors, such as contact with specific animal species, were significantly associated with ESBL-E/K carriage, whereas travel to Africa, Asia or Latin America in the past 6 months (OR 4.4), and stomach/bowel complaints in the past 4 weeks (OR 2.2) were. Sixteen of 33 initially ESBL-E/K positive participants (48.5%) tested positive again 6 months later, in 14 persons the same ESBL gene and E. coli ST was found. Four of 23 (17.4%) household members carried ESBL-E/K, in three persons this was the same ESBL gene and E. coli ST as in the veterinary healthcare worker.

Conclusions

Despite the absence of specific occupation related risk factors, ESBL-E/K carriage in veterinary healthcare workers was high compared to the prevalence in the general Dutch population (5%). This indicates that occupational contact with animals is a potential source of ESBL-E/K for the population at large.
Epidemiology of ESBL-producing Escherichia coli from repeated prevalence studies over 11 years in a long-term-care facility
Authors: Martischang Romain , François Patrice , Cherkaoui Abdessalam , Gaïa Nadia , Renzi Gesuele , Agostinho Americo , Perez Monica , Graf Christophe E. , Harbarth Stephan
Published: October 2021

Background

Escherichia colisequence type (ST) 131 H30 is an emerging multidrug resistant subclone, known to spread and cause outbreaks in long-term care facilities (LTCFs).

Objectives and methods

From 2010 through 2020, we performed 11 yearly surveillance studies for determining the prevalence of digestive carriage of ESBL-producingE. coli(ESBL-EC) among residents in a university-affiliated LCTF. Sequencing and genotyping of selected isolates were performed to characterize temporal trends in the prevalence and epidemic potential of ESBL-EC subclones, and for evaluating a potential rebound effect following discontinuation of contact precautions for ESBL-EC carriers in January 2019.

Results

This study included 2′403 LTCF residents, with 252 (10.5%) positive for ESBL-EC. Among the 236 ESBL-EC isolates available for typing, 58.0% belonged to the ST131 lineage, including 94/137 (68.6%) ST131 H30 isolates. An increasing yearly prevalence was observed for ESBL-EC (from 4.6 to 9.4%;p = 0.11), but not for the ST131 H30 subclone, which peaked in 2015 and declined thereafter. Multiple previously unnoticed ESBL-EC outbreaks occurred in the LTCF. Since 2018, we noted the clonal expansion of a rare ST131 H89 subclone (O16:H5) harboring CTX-M-14 and CTX-M-24. No rebound effect was observed in ESBL-EC prevalence nor in the different subclones following discontinuation of contact precautions for ESBL-EC carriers since 2019.

Conclusion

Clonal fluctuation was observed for ST131 H30 ESBL-EC with a current decline in prevalence. Surveillance should include the evolution of ST131 non-H30 subclones, which may spread in LTCFs. Our findings suggest that discontinuation of contact precautions for ESBL-EC carriers in LTCFs may be safely implemented, in support of European recommendations to limit ESBL-producing Enterobacteriaceae control measures in endemic settings to non-E. coli.
Duckweeds: their utilization, metabolites and cultivation
Authors: Baek GahYoung , Saeed Maham , Choi Hyung-Kyoon
Published: October 2021

Duckweeds are floating plants of the family Lemnaceae, comprising 5 genera and 36 species. They typically live in ponds or lakes and are found worldwide, except the polar regions. There are two duckweed subfamilies—namely Lemnoidea and Wolffioideae, with 15 and 21 species, respectively. Additionally, they have characteristic reproduction methods. Several metabolites have also been reported in various duckweeds. Duckweeds have a wide range of adaptive capabilities and are particularly suitable for experiments requiring high productivity because of their speedy growth and reproduction rates. Duckweeds have been studied for their use as food/feed resources and pharmaceuticals, as well as for phytoremediation and industrial applications. Because there are numerous duckweed species, culture conditions should be optimized for industrial applications. Here, we review and summarize studies on duckweed species and their utilization, metabolites, and cultivation methods to support the extended application of duckweeds in future.
Cell competition between wild-type and JAK2V617F mutant cells prevents disease relapse after stem cell transplantation in a murine model of myeloproliferative neoplasm
Authors: Zhang Haotian , Castiglione Melissa , Zheng Lei , Zhan Huichun
Published: October 2021

Disease relapse after allogeneic stem cell transplantation is a major cause of treatment-related morbidity and mortality in patients with myeloproliferative neoplasms (MPNs). The cellular and molecular mechanisms for MPN relapse are not well understood. Here, we established a murine model of MPN relapse, in which ~ 60% of the MPN recipient mice develop disease relapse after receiving stem cell transplantation with wild-type marrow donor. Using this model, we find that impaired wild-type cell function is associated with MPN disease relapse. We also show that competition between wild-type and JAK2V617F mutant cells can modulate the immune cell composition and PD-L1 expression induced by the JAK2V617F oncogene. These results suggest that cell competition between wild-type donor cells and JAK2V617F mutant recipient cells can prevent MPN disease relapse after stem cell transplantation.
A simple yet consistent constitutive law and mortar-based layer coupling schemes for thermomechanical macroscale simulations of metal additive manufacturing processes
Authors: Proell Sebastian D. , Wall Wolfgang A. , Meier Christoph
Published: October 2021

This article proposes a coupled thermomechanical finite element model tailored to the macroscale simulation of metal additive manufacturing processes such as selective laser melting. A first focus lies on the derivation of a consistent constitutive law on basis of a Voigt-type spatial homogenization procedure across the relevant phases, powder, melt and solid. The proposed constitutive law accounts for the irreversibility of phase change and consistently represents thermally induced residual stresses. In particular, the incorporation of a reference strain term, formulated in rate form, allows to consistently enforce a stress-free configuration for newly solidifying material at melt temperature. Application to elementary test cases demonstrates the validity of the proposed constitutive law and allows for a comparison with analytical and reference solutions. Moreover, these elementary solidification scenarios give detailed insights and foster understanding of basic mechanisms of residual stress generation in melting and solidification problems with localized, moving heat sources. As a second methodological aspect, dual mortar mesh tying strategies are proposed for the coupling of successively applied powder layers. This approach allows for very flexible mesh generation for complex geometries. As compared to collocation-type coupling schemes, e.g., based on hanging nodes, these mortar methods enforce the coupling conditions between non-matching meshes in an $$L^2$$

L
2

-optimal manner. The combination of the proposed constitutive law and mortar mesh tying approach is validated on realistic three-dimensional examples, representing a first step towards part-scale predictions.