bluuebunny/crossref_metadata_2025_split huggingface dataset:
From informed consent to adherence: factors influencing involvement in mass drug administration with ivermectin for malaria elimination in The Gambia
Authors: Fehr Alexandra , Nieto-Sanchez Claudia , Muela Joan , Jaiteh Fatou , Ceesay Omar , Maneh Ebrima , Baldeh Dullo , Achan Jane , Dabira Edgard , Conteh Bakary , Bunders-Aelen Joske , Smekens Tom , Broekhuizen Henk , D’Alessandro Umberto , Peeters Grietens Koen 
Published: April 2021

Abstract
Background
The World Health Organization (WHO) recommends consideration of mass drug administration (MDA) for malaria control in low-endemic settings approaching elimination. However, MDA remains a controversial strategy, as multiple individual, social, and operational factors have shown to affect its acceptability at local levels. This is further complicated by inconsistent definitions of key indicators derived from individual and community involvement—coverage, adherence, and compliance—that cast doubts about the actual and potential epidemiological impact of MDA on disease control and elimination. This study aimed to identify limitations and enabling factors impacting involvement at different stages of a large cluster-randomized trial assessing the effect of combining dihydroartemisinin-piperaquine (DP) and ivermectin (IVM) in malaria transmission in The Gambia.

Methods
This social science study used a mixed-methods approach. Qualitative data were collected in intervention and control villages through ethnographic methods, including in-depth interviews (IDIs), focus group discussions (FGDs), and participant observation conducted with trial participants and decliners, community leaders, and field staff. A cross-sectional survey was conducted in the intervention villages after the first year of MDA. Both strands of the study explored malaria knowledge and opinions, social dynamics influencing decision-making, as well as perceived risks, burdens, and benefits associated with this MDA.

Results
157 IDIs and 11 FGDs were conducted, and 864 respondents were included in the survey. Barriers and enabling factors to involvement were differentially influential at the various stages of the MDA. Issues of social influence, concerns regarding secondary effects of the medication, costs associated with malaria, and acceptability of the implementing organization, among other factors, differently affected the decision-making processes throughout the trial. Rather than a linear trajectory, involvement in this MDA trial was subjected to multiple revaluations from enrolment and consent to medicine intake and adherence to treatment.

Conclusions
This study went beyond the individual factors often associated with coverage and adherence, and found that nuanced social dynamics greatly influence the decision-making process at all phases of the trial. These issues need to be consider for MDA implementation strategies and inform discussions about more accurate ways of reporting on critical effectiveness indicators.
Fifteen-year trends in self-reported racism and link with health and well-being of African Canadian adolescents: a secondary data analysis
Authors: Okoye Helen U. , Saewyc Elizabeth 
Published: April 2021

Abstract
Background
We assessed the prevalence and trends in racial discrimination among African Canadian adolescents in British Columbia. The association between racial discrimination and self-rated health, access to mental health services, substance use, suicidal thoughts and attempts, experience of extreme stress, among others were examined within the 2018 dataset.

Methods
Secondary analysis used the data collected from African Canadian adolescents (n = 2448) as part of the British Columbia Adolescent Health Surveys (2003–2018). We examined whether racial discrimination increased, decreased, or remained stable over time. We evaluated experiences of racial discrimination for all adolescents, and then disaggregated analyses for boys, girls, immigrant, and Canadian-born African adolescents. We used Rao-Scott’s adjusted chi-square to test differences in racial discrimination and adjusted logistic regressions to test trends across survey years, widening or narrowing gaps in racial discrimination, as well as the link to health outcomes.

Results
Racial discrimination was significantly different across the survey years (Adjusted F = 4.60, p < .01), with the highest percentage of adolescents reporting past year racial discrimination in 2018 (29.9%) and the lowest percentage in 2013 (21.3%). Girls and immigrant African Canadian adolescents were more likely to have experienced racial discrimination. However, girls and Canadian-born adolescents had the highest odds of reporting racial discrimination in 2018 compared to 2003, AOR = 1.85, and 1.58, respectively. The findings reveal significant differences in the experiences of racial discrimination for boys and girls, as well as for immigrant and Canadian-born African adolescents. Significant differences were noted in the link between racial discrimination and self-rated health and engaging in behaviours that might expose them to health risks. The worst negative health outcomes were found for boys and immigrant African Canadian adolescents.

Conclusion
The study suggests that more than 1 in 4 African Canadian adolescents in British Columbia report racial discrimination, which is an increasing trend in recent years. Those who reported racial discrimination also had the worst adverse health outcomes. There is a need for more public health action to reduce racism, create awareness about the negative health impacts, and provide better support for African Canadian adolescents.
Impact of the COVID-19 pandemic on the food rations of refugees in Rwanda
Authors: Manirambona Emery , Uwizeyimana Theogene , Uwiringiyimana Emmanuel , Reddy Henna 
Published: April 2021

AbstractThe coronavirus disease (COVID-19) has significantly impacted the global economy, by forcing people to stay indoors and creating a ‘new normal’ of living. Rwanda has made notable efforts to fight the pandemic. However, the impacts of the COVID-19 pandemic on the country’s economy are numerous and the refugees residing in Rwanda are not spared these effects. As of December 2020, 164,000 people were granted refugee status in Rwanda according to the United Nations High Commissioner for Refugees (UNHCR). The majority were from neighbouring countries in the Great Lakes regions, including DRC (Democratic Republic of Congo) and Burundi. The impact the COVID-19 pandemic on the global economy has led to a decline in donations to the United Nations World Food Programme (WFP), which in turn has significantly reduced the food rations of refugees. Such paucity will no doubt cause unprecedented impacts on the people residing in refugee camps, who completely depend on humanitarian aid to meet their basic food requirements. This lack of access to adequate and affordable food will expose refugees to extreme hunger and starvation, putting their lives in danger by triggering forced returns, infections, social conflicts and thus higher morbidity and mortality.Furthermore, such stressful environments would no doubt put the mental health of these already vulnerable communities at risk. It is unsurprising that refugees are more likely to experience poor mental health compared to local population, including higher rates of depression and anxiety disorders including Post-Traumatic Stress Disorder (PTSD). This is an issue as they are also less likely to receive support than the general population. Refugees in Rwanda are under the responsibility of UNHCR and WFP, who should ensure adequate food assistance is provided to refugees and therefore ameliorate the risks to health that result from food shortages, safeguarding these vulnerable communities.
Elucidation of SIRT-1/PGC-1α-associated mitochondrial dysfunction and autophagy in nonalcoholic fatty liver disease
Authors: Jiang Yan , Chen Duankai , Gong Qiming , Xu Qunqing , Pan Dong , Lu Feiyan , Tang Qianli 
Published: April 2021

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) can lead to chronic liver diseases associated with mitochondrial damages. However, the exact mechanisms involved in the etiology of the disease are not clear.

Methods
To gain new insights, the changes affecting sirtuin 1 (SIRT-1) during liver fat accumulation was investigated in a NAFLD mouse model. In addition, the in vitro research investigated the regulation operated by SIRT-1 on mitochondrial structures, biogenesis, functions, and autophagy.

Results
In mice NAFLD, high-fat-diet (HFD) increased body weight gain, upregulated serum total cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, blood glucose, insulin levels, and liver malondialdehyde, and decreased liver superoxide dismutase activity. In liver, the levels of SIRT-1 and peroxisome proliferator-activated receptor-gamma coactivator -1α (PGC-1α) decreased. The expression of peroxisome proliferator-activated receptor-α and Beclin-1 proteins was also reduced, while p62/SQSTM1 expression increased. These results demonstrated SIRT-1 impairment in mouse NAFLD. In a well-established NAFLD cell model, exposure of the HepG2 hepatocyte cell line to oleic acid (OA) for 48 h caused viability reduction, apoptosis, lipid accumulation, and reactive oxygen species production. Disturbance of SIRT-1 expression affected mitochondria. Pre-treatment with Tenovin-6, a SIRT-1 inhibitor, aggravated the effect of OA on hepG2, while this effect was reversed by CAY10602, a SIRT-1 activator. Further investigation demonstrated that SIRT-1 activity was involved in mitochondrial biogenesis through PGC-1α and participated to the balance of autophagy regulatory proteins.

Conclusion
In conclusion, in high-fat conditions, SIRT-1 regulates multiple cellular properties by influencing on mitochondrial physiology and lipid autophagy via the PGC-1α pathway. The SIRT-1/PGC-1α pathway could be targeted to develop new NAFLD therapeutic strategies.
Transient cell stiffening triggered by magnetic nanoparticle exposure
Authors: Perez Jose E. , Fage Florian , Pereira David , Abou-Hassan Ali , Asnacios Sophie , Asnacios Atef , Wilhelm Claire 
Published: April 2021

Abstract
Background
The interactions between nanoparticles and the biological environment have long been studied, with toxicological assays being the most common experimental route. In parallel, recent growing evidence has brought into light the important role that cell mechanics play in numerous cell biological processes. However, despite the prevalence of nanotechnology applications in biology, and in particular the increased use of magnetic nanoparticles for cell therapy and imaging, the impact of nanoparticles on the cells’ mechanical properties remains poorly understood.

Results
Here, we used a parallel plate rheometer to measure the impact of magnetic nanoparticles on the viscoelastic modulus G*(f) of individual cells. We show how the active uptake of nanoparticles translates into cell stiffening in a short time scale (< 30 min), at the single cell level. The cell stiffening effect is however less marked at the cell population level, when the cells are pre-labeled under a longer incubation time (2 h) with nanoparticles. 24 h later, the stiffening effect is no more present. Imaging of the nanoparticle uptake reveals almost immediate (within minutes) nanoparticle aggregation at the cell membrane, triggering early endocytosis, whereas nanoparticles are almost all confined in late or lysosomal endosomes after 2 h of uptake. Remarkably, this correlates well with the imaging of the actin cytoskeleton, with actin bundling being highly prevalent at early time points into the exposure to the nanoparticles, an effect that renormalizes after longer periods.

Conclusions
Overall, this work evidences that magnetic nanoparticle internalization, coupled to cytoskeleton remodeling, contributes to a change in the cell mechanical properties within minutes of their initial contact, leading to an increase in cell rigidity. This effect appears to be transient, reduced after hours and disappearing 24 h after the internalization has taken place.
Fluorochloridone induces autophagy in TM4 Sertoli cells: involvement of ROS-mediated AKT-mTOR signaling pathway
Authors: Ni Zhijing , Sun Weiqi , Li Rui , Yang Mingjun , Zhang Fen , Chang Xiuli , Li Weihua , Zhou Zhijun 
Published: April 2021

Abstract
Background
Fluorochloridone (FLC), a selective pyrrolidone herbicide, has been recognized as a potential endocrine disruptor and reported to induce male reproductive toxicity, but the underlying mechanism is unclear. The aim of this study was to investigate the mechanism of FLC-induced reproductive toxicity on male mice with particular emphasis on the role of autophagy in mice’ TM4 Sertoli cells.

Methods
Adult C57BL/6 mice were divided into one control group (0.5% sodium carboxymethyl cellulose), and four FLC-treated groups (3,15,75,375 mg/kg). The animals (ten mice per group) received gavage for 28 days. After treatment, histological analysis, sperm parameters, the microstructure of autophagy and the expression of autophagy-associated proteins in testis were evaluated. Furthermore, to explore the autophagy mechanism, TM4 Sertoli cells were treated with FLC (0,40,80,160 μM) in vitro for 24 h. Cell activity and cytoskeletal changes were measured by MTT assay and F-actin immunofluorescence staining. The formation of autophagosome, accumulation of reactive oxygen species (ROS), expression of autophagy marker proteins (LC3, Beclin-1 and P62) and AKT-related pathway proteins (AKT, mTOR) were observed. The ROS scavenger N-acetylcysteine (NAC) and AKT agonist (SC79) were used to treat TM4 cells to observe the changes of AKT-mTOR pathway and autophagy.

Results
In vivo, it showed that FLC exposure caused testicular injuries, abnormality in epididymal sperm. Moreover, FLC increased the formation of autophagosomes, the accumulation of LC3II/LC3I, Beclin-1 and P62 protein, which is related to the degradation of autophagy. In vitro, FLC triggered TM4 cell autophagy by increasing the formation of autophagosomes and upregulating of LC3II/LC3I, Beclin-1 and P62 levels. In addition, FLC induced ROS production and inhibited the activities of AKT and mTOR kinases. The Inhibition of AKT/mTOR signaling pathways and the activation of autophagy induced by FLC could be efficiently reversed by pretreatment of NAC. Additionally, decreased autophagy and increased cell viability were observed in TM4 cells treated with SC79 and FLC, compared with FLC alone, indicating that FLC-induced autophagy may be pro-death.

Conclusion
Taken together, our study provided the evidence that FLC promoted autophagy in TM4 Sertoli cells and that this process may involve ROS-mediated AKT/mTOR signaling pathways.
Is immunotherapy in the future of therapeutic management of sarcomas?
Authors: Clemente Ottavia , Ottaiano Alessandro , Di Lorenzo Giuseppe , Bracigliano Alessandra , Lamia Sabrina , Cannella Lucia , Pizzolorusso Antonio , Di Marzo Massimiliano , Santorsola Mariachiara , De Chiara Annarosaria , Fazioli Flavio , Tafuto Salvatore 
Published: April 2021

AbstractSarcomas are rare, ubiquitous and heterogeneous tumors usually treated with surgery, chemotherapy, target therapy, and radiotherapy. However, 25–50% of patients experience local relapses and/or distant metastases after chemotherapy with an overall survival about 12–18 months. Recently, immuno-therapy has revolutionized the cancer treatments with initial indications for non-small cell lung cancer (NSCLC) and melanoma (immune-checkpoint inhibitors).Here, we provide a narrative review on the topic as well as a critical description of the currently available trials on immunotherapy treatments in patients with sarcoma. Given the promising results obtained with anti-PD-1 monoclonal antibodies (pembrolizumab and nivolumab) and CAR-T cells, we strongly believe that these new immunotherapeutic approaches, along with an innovative characterization of tumor genetics, will provide an exciting opportunity to ameliorate the therapeutic management of sarcomas.
Deregulation of IL-37 and its miRNAs modulators in sarcopenic patients after rehabilitation
Authors: La Rosa Francesca , Agostini Simone , Saresella Marina , Costa Andrea Saul , Piancone Federica , Miglioli Rossella , Trecate Fabio , Clerici Mario 
Published: April 2021

AbstractBackgroundsarcopenia is a highly prevalent condition in elderly individuals which is characterized by loss of muscle mass and functions; recent results showed that it is also associated with inflammation. Rehabilitation protocols for sarcopenia are designed to improve physical conditions, but very scarce data are available on their effects on inflammation We verified whether in sarcopenic patients the inflammation is reduced by rehabilitation and investigated the biological correlates of such effect.MethodsTwenty-one sarcopenic patients undergoing a specifically-designed rehabilitation program were enrolled in the study. Physical, cognitive and nutritional parameters, as well as the concentration of C-Reactive Protein (CRP), pro-and anti-inflammatory cytokines and cytokine production-modulating miRNAs were measured at the beginning (T0) and at end (30-days; T1) of the rehabilitation.ResultsRehabilitation resulted in a significant improvement of physical and cognitive conditions; this was accompanied by a significant reduction of CRP (p = 0.04) as well as of IL-18 (p = 0.008) and IL-37 (p = 0.009) concentration. Notably, the concentration of miR-335-3p (p = 0.007) and miR-657, the two known post-transcriptional regulators of IL-37 production, was increased by the rehabilitation protocol.ConclusionsResults herein confirm that successful rehabilitation for sarcopenia results in a reduction of the inflammatory milieu, raise the possibility that IL-37 may be a key target to monitor the rehabilitation-associated improvement in sarcopenia, and suggest that this cytokine could be a therapeutic target in sarcopenic patients.
Monoclonal antibodies specific for the hemagglutinin-neuraminidase protein define neutralizing epitopes specific for Newcastle disease virus genotype 2.VII from Egypt
Authors: Moharam Ibrahim , Asala Olayinka , Reiche Sven , Hafez Hafez , Beer Martin , Harder Timm , Grund Christian 
Published: April 2021

Abstract
Background
Newcastle disease is a devastating disease in poultry caused by virulent Newcastle disease virus (NDV), a paramyxovirus endemic in many regions of the world despite intensive vaccination. Phylogenetic analyses reveal ongoing evolution of the predominant circulating genotype 2.VII, and the relevance of potential antigenic drift is under discussion. To investigate variation within neutralization-sensitive epitopes within the protein responsible for receptor binding, i.e. the Hemagglutinin-Neuraminidase (HN) spike protein, we were interested in establishing genotype-specific monoclonal antibodies (MAbs).

Methods
An HN-enriched fraction of a gradient-purified NDV genotype 2.VII was prepared and successfully employed to induce antibodies in BalbC mice that recognize conformationally intact sites reactive by haemagglutination inhibition (HI). For subsequent screening of mouse hybridoma cultures, an NDV-ELISA was established that utilizes Concanavalin A (ConA-ELISA) coupled glycoproteins proven to present conformation-dependent epitopes.

Results
Six out of nine selected MAbs were able to block receptor binding as demonstrated by HI activity. One MAb recognized an epitope only present in the homologue virus, while four other MAbs showed weak reactivity to selected other genotypes. On the other hand, one broadly cross-reacting MAb reacted with all genotypes tested and resembled the reactivity profile of genotype-specific polyclonal antibody preparations that point to minor antigenic differences between tested NDV genotpyes.

Conclusions
These results point to the concurrent presence of variable and conserved epitopes within the HN molecule of NDV. The described protocol should help to generate MAbs against a variety of NDV strains and to enable in depth analysis of the antigenic profiles of different genotypes.
Contested or complementary healing paradigms? Women’s narratives of COVID-19 remedies in Mwanza, Tanzania
Authors: Mshana Gerry , Mchome Zaina , Aloyce Diana , Peter Esther , Kapiga Saidi , Stöckl Heidi 
Published: April 2021

Abstract
Background
COVID-19 has caused worldwide fear and uncertainty. Historically, the biomedical disease paradigm established its dominance in tackling emerging infectious illnesses mainly due to innovation in medication and advances in technology. Traditional and religious remedies have emerged as plausible options for prevention and treatment of COVID-19, especially in Africa and Asia. The appeal of religious and traditional therapies against COVID-19 in the African setting must be understood within the historical, social, and political context. This study explored how women and community members dealt with suspected symptoms of COVID-19 in Mwanza, Tanzania.

Methods
This study was conducted in Nyamagana and Ilemela districts of Mwanza, Tanzania, between July and August 2020. We conducted 18 mobile phone in-depth interviews with a purposively selected sample of women aged 27–57 years participating in an existing longitudinal study. For safety reasons, smart mobile phones were used to collect the data. Each interview was audio recorded after obtaining verbal consent from the participants. The audio files were transferred to computers for analysis. Four researchers conducted a multistage, inductive analysis of the data.

Results
Participants reported wide use and perceived high efficacy of traditional remedies and prayer to prevent and treat suspected symptoms of COVID-19. Use was either alone or combined with public health recommendations such as hand washing and crowd avoidance. Despite acknowledging that a pathogen causes COVID-19, participants attested to the relevance and power of traditional herbal medication and prayer to curb COVID-19. Four main factors underline the symbolic efficacy of the traditional and religious treatment paradigms: personal, communal, and official reinforcement of their efficacy; connection to local knowledge and belief systems; the failure of biomedicine to offer a quick and effective solution; and availability.

Conclusions
In the context of emerging contagious illnesses, communities turn to resilient and trusted treatment paradigms to quell fear and embrace hope. To tackle emerging infections effectively, it is essential to engage the broader sociopolitical landscape, including communal considerations of therapeutic efficacy.