bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a roadmap for mainstreaming nutrition-sensitive interventions at state level in Nigeria
Authors: Ezekannagha Oluchi , Drimie Scott , von Fintel Dieter , Maziya-Dixon Busie , Mbhenyane Xikombiso 
Published: September 2020

Abstract
Background
National programs are often developed with little consideration to the sub-national local factors that might affect program success. These factors include political support, capacity for implementation of program and variation in malnutrition indices being tackled. State context factors are evident in the distribution of malnutrition (e.g. high prevalence or gap among Local Government Areas), in the implementation of nutrition-sensitive interventions (e.g. access to early childhood education) and in the political economic context (e.g. presence of external funding agencies). Context is shaped by the economy, population, religion, and poverty, which impact everyday lives. Considering these contexts, a roadmap was developed and validated. The aim of this paper is to report expert review and stakeholder validation to determine feasibility of the developed contextualised roadmap for two Nigerian states.

Methods
A validation tool was developed and reviewed using three experts. The content review occurred in two rounds to obtain recommendation and revisions of the developed roadmap and the validation tool. A pilot test of the roadmap and validation tool was done using two stakeholders in South Africa. The roadmap and the validation tool were then sent to the stakeholders and potential end-users in Nigeria using electronic media. Two research assistants were also engaged to deliver and collect hard copies to those who preferred it.

Results
Of the ten stakeholders invited, nine responded. All participants showed an adequate understanding of the roadmap as evidenced by the scores given. Responses regarding the translation of the roadmap to implementation varied. The majority (86,6%) either strongly agreed or agreed that the actions were translatable (43.0 and 43.6% respectively).

Conclusions
The final roadmap comprises of actions that are appropriate for the state’s context. It is recommended that stakeholders or end-users of any programme must be involved in the validation of such contextual programmes to improve chances of success.
A scoping review of policies promoting and supporting sustainable food systems in the university setting
Authors: Grech Amanda , Howse Eloise , Boylan Sinead 
Published: September 2020

Abstract
Background
Transitioning towards sustainable food systems for the health of the population and planet will require governments and institutions to develop effective governance to support the adoption of sustainable food practices. The aim of the paper is to describe current governance within Australian and New Zealand universities designed to support sustainable food systems.

Methods
A systematic search of governance documents to support sustainable food systems within Australian and New Zealand universities was conducted. Data were obtained from 1) targeted websites 2) internet search engines and 3) expert consultations. Inclusion criteria consisted of university governance documents including by-laws, policies, guidelines, frameworks, and procedures that support sustainable food systems.

Results
Twenty-nine governance documents across nineteen Australian and New Zealand universities were included for synthesis, including waste management policies (n = 3), fair-trade/procurement policies (n = 6), catering and or event guidelines (n = 7) and catering policies (n = 2), and environmental management plans (n = 11). The main strategies adopted by universities were sustainable waste management and prevention (e.g. reducing landfill, reducing wasted food, (27%)), ethical procurement practices (i.e. fair-trade (27%)) and environmentally sustainable food consumption (e.g. local, seasonal, organic, vegetarian food supply (14.5%)). Only 12.5% of universities addressed all three of the main strategies identified.

Conclusions
This study indicates that while sustainable food systems are considered in some university governance documents, efforts are predominantly focused on aspects such as waste management or procurement of fair-trade items which as stand-alone practices are likely to have minimal impact. This review highlights the scope of universities to provide strong leadership in promoting and supporting sustainable food systems through holistic institutional policies and governance mechanisms.
Coping with the COVID-19 pandemic – the role of leadership in the Arab ethnic minority in Israel
Authors: Saban Mor , Myers Vicki , Wilf-Miron Rachel 
Published: September 2020

Abstract
Background
The Arab ethnic minority makes up 21% of Israel’s population, yet comprised just 8.8% of confirmed cases and 3.6% of deaths from COVID-19, despite their higher risk profile and greater burden of underlying illness. This paper presents differences in patterns of morbidity and mortality from COVID-19 in the Arab, ultra-Orthodox and overall populations in Israel, and suggests possible reasons for the low rates of infection in the Arab population.

Methods
Data were obtained from the Israeli Ministry of Health’s (MOH) open COVID-19 database, which includes information on 1270 localities and is updated daily. The database contains the number of COVID-19 diagnostic tests performed, the number of confirmed cases and deaths in Israel.

Results
In the first 4 months of Israel’s COVID-19 outbreak, just 2060 cases were confirmed in the Arab population, comprising 8.8% of the 23,345 confirmed cases, or 2.38 times less than would be expected relative to the population size. In contrast, the ultra-Orthodox made up 30.1% of confirmed cases yet just 10.1% of the population. Confirmed case rate per 100,000 was twice as high in the general Jewish population compared to the Arab population. The Arab mortality rate was 0.57 per 100,000, compared to 3.37 in the overall population, and to 7.26 in the ultra-Orthodox community. We discuss possible reasons for this low morbidity and mortality including less use of nursing homes, and effective leadership which led to early closure of mosques and high adherence to social distancing measures, even during the month of Ramadan.

Conclusions
Despite a disproportionate burden of underlying illness, the Arab population did not fulfil initial predictions during the first wave of the COVID-19 outbreak and maintained low numbers of infections and deaths. This contrasts with reports of increased mortality in ethnic minorities and economically disadvantaged populations in other countries, and with high rates of infection in the ultra-Orthodox sector in Israel. Effective leadership and cooperation between individuals and institutions, particularly engagement of community and religious leaders, can reduce a group’s vulnerability and build resilience in an emergency situation such as the current pandemic.
Loss of FBXW7-mediated degradation of BRAF elicits resistance to BET inhibitors in adult T cell leukemia cells
Authors: Yeh Chien-Hung , Bellon Marcia , Wang Fang , Zhang Hong , Fu Liwu , Nicot Christophe 
Published: September 2020

Abstract
Background
Human T cell leukemia virus type 1 (HTLV-1)-associated adult T cell leukemia (ATL) has a very poor prognosis with a median survival of 8 months and a 4-year overall survival of 11% for acute ATL. Present treatment options are limited and there is no curative therapy for ATL. Ubiquitin ligase FBXW7 is commonly mutated or functionally inactivated in human cancers. Consistent with the notion that FBXW7 controls the degradation of many oncoproteins, loss of FBXW7 has been linked to increased drug resistance or sensitivity in cancer cells.

Method
In this study, we have characterized FBXW7 mutants previously identified in HTLV-I-infected ATL patient samples. TET-inducible ATL cells carrying wild type or mutated FBXW7 were analyzed for target degradation and for drug sensitivity.

Results
Our results demonstrate that mutations in FBXW7 can selectively disrupt ubiquitination and proteasome degradation of target proteins: c-MYC, cyclin E and MCL1. Both c-MYC and MYCN were highly expressed in uncultured ATL patient’s samples and ATL-derived cell lines; and ATL cells demonstrated sensitivity to BET inhibitors in vitro and in vivo. High-throughput reverse phase protein array revealed BRAF as a novel target of FBXW7 and further experiments showed that mutations in FBXW7 preventing degradation of BRAF provided resistance to BET inhibitors. In contrast to R465, hot spot FBXW7 mutations at R505C retained degradation of BRAF but not NOTCH1, c-MYC, cyclin E, or MCL1. Finally, a combination therapy using BET inhibitors along with a BRAF or an ERK inhibitor prevented tumor cell resistance and growth.

Conclusion
Our results suggest that FBXW7 status may play an important role in drug therapy resistance of cancer cells. Genetic characterization of FBXW7 may be one factor included in future personalized cancer treatment identification.
Multiparametric investigation of non functionalized-AGuIX nanoparticles in 3D human airway epithelium models demonstrates preferential targeting of tumor cells
Authors: Sancey Lucie , Sabido Odile , He Zhiguo , Rossetti Fabien , Guignandon Alain , Bin Valérie , Coll Jean-Luc , Cottier Michèle , Lux François , Tillement Olivier , Constant Samuel , Mas Christophe , Boudard Delphine 
Published: September 2020

AbstractLiquid deposit mimicking surface aerosolization in the airway is a promising strategy for targeting bronchopulmonary tumors with reduced doses of nanoparticle (NPs). In mimicking and studying such delivery approaches, the use of human in vitro 3D culture models can bridge the gap between 2D cell culture and small animal investigations. Here, we exposed airway epithelia to liquid-apical gadolinium-based AGuIX® NPs in order to determine their safety profile. We used a multiparametric methodology to investigate the NP’s distribution over time in both healthy and tumor-bearing 3D models. AGuIX® NPs were able to target tumor cells in the absence of specific surface functionalization, without evidence of toxicity. Finally, we validated the therapeutic potential of this hybrid theranostic AGuIX® NPs upon radiation exposure in this model. In conclusion, 3D cell cultures can efficiently mimic the normal and tumor-bearing airway epitheliums, providing an ethical and accessible model for the investigation of nebulized NPs.
LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP
Authors: Hu Lin , Wang Jing , Wang Yunliang , Wu Linpeng , Wu Chao , Mao Bo , Maruthi Prasad E. , Wang Yuhong , Chin Y. Eugene 
Published: September 2020

Abstract
Background
LOX-like 1 (LOXL1) is a lysyl oxidase, and emerging evidence has revealed its effect on malignant cancer progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated.

Methods
LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blotting and real-time PCR. In vitro, colony formation, wound healing, migration and invasion assays were performed to investigate the effects of LOXL1 on cell proliferation, migration and invasion. In vivo, metastasis models and mouse xenografts were used to assess tumorigenicity and metastasis ability. Molecular biology experiments were utilized to reveal the underlying mechanisms by which LOXL1 modulates the Hippo pathway.

Results
LOXL1 was highly expressed in normal colon tissues compared with cancer tissues. In vitro, silencing LOXL1 in CRC cell lines dramatically enhanced migration, invasion, and colony formation, while overexpression of LOXL1 exerted the opposite effects. The results of the in vivo experiments demonstrated that the overexpression of LOXL1 in CRC cell lines drastically inhibited metastatic progression and tumour growth. Mechanistically, LOXL1 inhibited the transcriptional activity of Yes-associated protein (YAP) by interacting with MST1/2 and increasing the phosphorylation of MST1/2.

Conclusions
LOXL1 may function as an important tumour suppressor in regulating tumour growth, invasion and metastasis via negative regulation of YAP activity.

Graphical abstract
Caspase-1 has a critical role in blood-brain barrier injury and its inhibition contributes to multifaceted repair
Authors: Israelov Hila , Ravid Orly , Atrakchi Dana , Rand Daniel , Elhaik Shirin , Bresler Yael , Twitto-Greenberg Rachel , Omesi Liora , Liraz-Zaltsman Sigal , Gosselet Fabien , Schnaider Beeri Michal , Cooper Itzik 
Published: September 2020

AbstractBackgroundExcessive inflammation might activate and injure the blood-brain barrier (BBB), a common feature of many central nervous system (CNS) disorders. We previously developed an in vitro BBB injury model in which the organophosphate paraoxon (PX) affects the BBB endothelium by attenuating junctional protein expression leading to weakened barrier integrity. The objective of this study was to investigate the inflammatory cellular response at the BBB to elucidate critical pathways that might lead to effective treatment in CNS pathologies in which the BBB is compromised. We hypothesized that caspase-1, a core component of the inflammasome complex, might have important role in BBB function since accumulating evidence indicates its involvement in brain inflammation and pathophysiology.MethodsAn in vitro human BBB model was employed to investigate BBB functions related to inflammation, primarily adhesion and transmigration of peripheral blood mononuclear cells (PBMCs). Caspase-1 pathway was studied by measurements of its activation state and its role in PBMCs adhesion, transmigration, and BBB permeability were investigated using the specific caspase-1 inhibitor, VX-765. Expression level of adhesion and junctional molecules and the secretion of pro-inflammatory cytokines were measured in vitro and in vivo at the BBB endothelium after exposure to PX. The potential repair effect of blocking caspase-1 and downstream molecules was evaluated by immunocytochemistry, ELISA, and Nanostring technology.ResultsPX affected the BBB in vitro by elevating the expression of the adhesion molecules E-selectin and ICAM-1 leading to increased adhesion of PBMCs to endothelial monolayer, followed by elevated transendothelial-migration which was ICAM-1 and LFA-1 dependent. Blocking caspase-8 and 9 rescued the viability of the endothelial cells but not the elevated transmigration of PBMCs. Inhibition of caspase-1, on the other hand, robustly restored all of barrier insults tested including PBMCs adhesion and transmigration, permeability, and VE-cadherin protein levels. The in vitro inflammatory response induced by PX and the role of caspase-1 in BBB injury were corroborated in vivo in isolated blood vessels from hippocampi of mice exposed to PX and treated with VX-765.ConclusionsThese results shed light on the important role of caspase-1 in BBB insult in general and specifically in the inflamed endothelium, and suggest therapeutic potential for various CNS disorders, by targeting caspase-1 in the injured BBB.
Returning of antiretroviral medication dispensed over a period of 8 months suggests non-adherence despite full adherence according to real time medication monitoring
Authors: Ngowi Kennedy Michael , Masika Lydia , Lyamuya Furaha , Muro Eva , Mmbaga Blandina T. , Sprangers Mirjam A. G. , Nieuwkerk Pythia T. , Aarnoutse Rob E. , Reiss Peter , Sumari-de Boer I. Marion 
Published: September 2020

AbstractReal-time medication monitoring (RTMM) may potentially enhance adherence to antiretroviral treatment (ART). We describe a participant in an ongoing trial who, shortly after completing trial participation, died of cryptococcal meningitis despite high levels of adherence according to self-report, pill-counts and RTMM (> 99%). However, she evidenced consistently high HIV viral load throughout the 48-week study follow-up. Subsequently, her relatives unsolicitedly returned eight months’ dispensed ART medication that she was supposed to have taken. This brief report illustrates the challenges of adherence measurements including RTMM, and reinforces the need to combine adherence assessments with viral load monitoring in HIV care.
In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2
Authors: Signer Johanna , Jonsdottir Hulda R. , Albrich Werner C. , Strasser Marc , Züst Roland , Ryter Sarah , Ackermann-Gäumann Rahel , Lenz Nicole , Siegrist Denise , Suter Andreas , Schoop Roland , Engler Olivier B. 
Published: September 2020

Abstract
Background
Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but outbreaks of Middle East Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV-1, and the recently identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 4 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections. Therefore we investigated the virucidal and antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E, highly pathogenic MERS- and SARS-CoVs, as well as the newly identified SARS-CoV-2, in vitro.

Methods
To evaluate the antiviral potential of the extract, we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract after infection to further evaluate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce® in re-constituted nasal epithelium.

Results
In the current study, we found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce® at 3.2 μg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 μg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. The observed virucidal activity of Echinaforce® was not restricted to common cold coronaviruses, as both SARS-CoV-1 and MERS-CoVs were inactivated at comparable concentrations. Finally, the causative agent of COVID-19, SARS-CoV-2 was also inactivated upon treatment with 50μg/ml Echinaforce®.

Conclusions
These results show that Echinaforce® is virucidal against HCoV-229E, upon direct contact and in an organotypic cell culture model. Furthermore, MERS-CoV and both SARS-CoV-1 and SARS-CoV-2 were inactivated at similar concentrations of the extract. Therefore we hypothesize that Echinacea purpurea preparations, such as Echinaforce®, could be effective as prophylactic treatment for all CoVs due to their structural similarities.
Radiation-induced lung toxicity – cellular and molecular mechanisms of pathogenesis, management, and literature review
Authors: Käsmann Lukas , Dietrich Alexander , Staab-Weijnitz Claudia A. , Manapov Farkhad , Behr Jürgen , Rimner Andreas , Jeremic Branislav , Senan Suresh , De Ruysscher Dirk , Lauber Kirsten , Belka Claus 
Published: September 2020

AbstractLung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on radiotherapy as a major part of multi-modality care, and treatment-related toxicities, such as radiation-induced pneumonitis and/or lung fibrosis, are important dose limiting factors with direct impact on patient outcomes and quality of life. In this review, we summarize the current understanding of radiation-induced pneumonitis and pulmonary fibrosis, present predictive factors as well as recent diagnostic and therapeutic advances. Novel candidates for molecularly targeted approaches to prevent and/or treat radiation-induced pneumonitis and pulmonary fibrosis are discussed.
Minimum 3.5-year outcomes of operative treatment for Achilles tendon partial tears in the midportion and retrocalcaneal area
Authors: Lohrer Heinz 
Published: September 2020

AbstractBackgroundAchilles tendon partial tears are not easy to diagnose and to manage. Most frequently, they are located in the midportion and insertional area. These entities result from different pathologic pathways, and different treatment strategies are applied. The outcome is rarely investigated.MethodsThis study includes patients who underwent surgery for partial tears in the midportion or retrocalcaneal Achilles tendon area between the years 2009 and 2015 by a single surgeon. Patients were prospectively assessed preoperatively and 3, 6, and 12 months postoperatively, using the VISA-A-G questionnaire. The final retrospective follow-up was performed after a minimum of 3.5 years postoperatively. Forty-eight Achilles tendon partial tears at the level of the retrocalcaneal bursa (impingement lesions) and 27 midportion Achilles tendon partial tears were identified. After applying rigorous exclusion criteria, 21 and 16 cases, respectively, remained for the final follow-up. Results were analysed by inferential and descriptive statistics.ResultsThe VISA-A-G outcome scores improved significantly from preoperative to 6 months, 12 months, and final postoperative assessment. Preoperatively, the average VISA-A-G score was 42.1 (range, 18–73) for patients operated for Achilles tendon partial tears at the level of the retrocalcaneal bursa and 44.6 (range, 10–73) for the midportion Achilles tendon partial tear group, respectively. At final follow-up 88.8 (range, 15 to 100) and 96.9 (range, 71 to 100) were scored in the respective treatment groups. A repeated measures ANOVA determined that mean performance levels showed a statistically significant difference between measurements (p< 0.001). There was no systematic effect found between groups (p= 0.836).ConclusionsIn Achilles tendon partial tears recalcitrant to conservative treatment, operative intervention is highly successful in most cases, irrespective of the level of the injury. Results were statistically equal when comparing the midportion and retrocalcaneal Achilles tendon partial tear groups.Trial registrationDRKS, DRKS00014266. Registered 06 April 2018. ‘Retrospectively registered’,https://www.drks.de/drks_web/navigate.do?navigationId=results.