bluuebunny/crossref_metadata_2025 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

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

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

The 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

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

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

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

Sarcomas 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

Background

sarcopenia 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.

Methods

Twenty-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.

Results

Rehabilitation 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.

Conclusions

Results 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.
Retraction Note to: Intra-articular injection in the knee of adipose derived stromal cells (stromal vascular fraction) and platelet rich plasma for osteoarthritis
Authors: Bansal Himanshu , Comella Kristin , Leon Jerry , Verma Poonam , Agrawal Diwaker , Koka Prasad , Ichim Thomas
Published: April 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12967-021-02852-z
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

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

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.
Use of alcohol, tobacco, cannabis, and other substances during the first wave of the SARS-CoV-2 pandemic in Europe: a survey on 36,000 European substance users
Authors: Manthey Jakob , Kilian Carolin , Carr Sinclair , Bartak Miroslav , Bloomfield Kim , Braddick Fleur , Gual Antoni , Neufeld Maria , O’Donnell Amy , Petruzelka Benjamin , Rogalewicz Vladimir , Rossow Ingeborg , Schulte Bernd , Rehm Jürgen
Published: April 2021

Background

SARS-CoV-2 reached Europe in early 2020 and disrupted the private and public life of its citizens, with potential implications for substance use. The objective of this study was to describe possible changes in substance use in the first months of the SARS-CoV-2 pandemic in Europe.

Methods

Data were obtained from a cross-sectional online survey of 36,538 adult substance users from 21 European countries conducted between April 24 and July 22 of 2020. Self-perceived changes in substance use were measured by asking respondents whether their use had decreased (slightly or substantially), increased (slightly or substantially), or not changed during the past month. The survey covered alcohol (frequency, quantity, and heavy episodic drinking occasions), tobacco, cannabis, and other illicit drug use. Sample weighted data were descriptively analysed and compared across substances.

Results

Across all countries, use of all substances remained unchanged for around half of the respondents, while the remainder reported either a decrease or increase in their substance use. For alcohol use, overall, a larger proportion of respondents indicated a decrease than those reporting an increase. In contrast, more respondents reported increases in their tobacco and cannabis use during the previous month compared to those reporting decreased use. No distinct direction of change was reported for other substance use.

Conclusions

Our findings suggest changes in use of alcohol, tobacco and cannabis during the initial months of the pandemic in several European countries. This study offers initial insights into changes in substance use. Other data sources, such as sales statistics, should be used to corroborate these preliminary findings.
Is fidelity to a complex behaviour change intervention associated with patient outcomes? Exploring the relationship between dietitian adherence and competence and the nutritional status of intervention patients in a successful stepped-wedge randomised clinical trial of eating as treatment (EAT)
Authors: Beck Alison K. , Baker Amanda L. , Carter Gregory , Robinson Laura , McCarter Kristen , Wratten Christopher , Bauer Judith , Wolfenden Luke , Britton Benjamin
Published: April 2021

Background

Behavioural medicine is characterised by findings for the effectiveness and efficacy of complex behaviour change interventions. Comparatively, scant attention has been paid to key intervention components or mechanisms of action. Evaluating relationships between process variables (fidelity) and intervention effects is central to addressing this imbalance. Accordingly, in the current study, we sought to explore the magnitude and direction of effect between fidelity predictors (dietitian adherence and competence) and intervention effects (patient nutritional status) during the intervention phase of a real-world, stepped-wedge evaluation of ‘EAT: Eating As Treatment’.

Methods

The EAT clinical trial was conducted within five major Australian hospitals located in Queensland, Western Australia, Victoria and South Australia between 2013 and 2016. EAT is a dietitian-delivered health behaviour change intervention designed to reduce malnutrition in head and neck cancer (HNC) patients undergoing radiotherapy. Dietitian adherence and competence ratings were derived from a 20% random sample of audio-recorded dietetic consultations (n=194) conducted after dietitians (n=18) were trained in EAT. Sessions were coded by trained, independent, coders using a study checklist, the Behaviour Change Counselling Index (BECCI) and items from the Cognitive Therapy Scale-Revised (CTS-R). Patient nutritional status was measured using the Patient-Generated Subjective Global Assessment (PGSGA).

Results

Dietitian adherence to a written nutrition plan (β=7.62, 95% CI=0.65 to 14.58,p=0.032), dietitian adherence to behaviour change counselling (β=0.69, 95% CI =0.02 to 1.38,p=0.045) and competence in delivering behaviour change counselling (β=3.50, 95% CI =0.47 to 6.53,p=0.024) were significant predictors of patient nutritional status. Dietitian adherence and competence ratings were higher during consultations with intervention patients at greater risk of malnutrition.

Conclusions

This study contributes new insights into the relationship between fidelity and treatment outcome by demonstrating that dietitian adherence and competence is greater when working with more challenging patients. This is likely central to the demonstrated success of the EAT intervention in reducing malnutrition and highlights the importance of ensuring that providers are adequately equipped to flexibly integrate intervention elements according to patient need.

Trial registration

This study is a process analysis of a stepped-wedge randomised controlled trial prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12613000320752; Date of registration 21/03/2013).
Curculigoside promotes osteogenic differentiation of ADSCs to prevent ovariectomized-induced osteoporosis
Authors: You Wei-Li , Xu Zheng-Long
Published: April 2021

Background

Curculigoside is a natural phenolic glycoside compound produced by Curculigo orchioides Gaertn. This study aimed to explore the effects of curculigoside in promoting the osteogenic differentiation of adipose-derived stem cells (ADSCs) as well as the underlying mechanism.

Methods

ADSCs were treated with curculigoside at different concentrations (0 μmol/L, 1 μmol/L, 2.5 μmol/L, 5 μmol/L, 10 μmol/L, and 20 μmol/L), and cell viability was assessed by CCK-8 assay. Then, the alkaline phosphatase (ALP) activity was determined, and alizarin red S (ARS) staining was performed to measure the extracellular mineralization of curculigoside. Information about protein-chemical interactions is provided by the search tool for interactions of chemicals (STITCH) database. Then, LY294002 was administered to explore the mechanism by which curculigoside promotes the osteogenic differentiation of ADSCs. Western blot assays were performed to assess changes in the expression of osteogenic-related markers and the phosphorylation of PI3K and AKT. Finally, we established an ovariectomized (OVX)-induced osteoporosis mouse model and administered curculigoside to explore the effects of curculigoside in preventing bone loss in vivo.

Results

The CCK-8 assay indicated that curculigoside did not induce cytotoxicity at a concentration of 5 μmol/L after 48 h. The ALP and ARS results revealed that the induced group had higher ALP activity and calcium deposition than the control group. Moreover, the curculigoside group exhibited increased biomineralization, ALP activity, and ARS staining compared to the induced and control groups, and these effects were partially inhibited by LY294002. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the target genes of curculigoside were mainly involved in the PI3K-Akt signaling pathway. PCR and western blot analysis showed that the expression of RUNX2, ALP, and Osterix was upregulated in curculigoside-treated ADSCs, but this effect was partially reversed by the PI3K inhibitor LY294002. Moreover, the curculigoside-treated group exhibited significantly increased phosphorylation of AKT to P-AKT compared with the osteogenic induction group. After treatment with curculigoside, the mice had a higher bone volume than the OVX mice, suggesting partial protection from cancellous bone loss. In addition, when LY294002 was added, the protective effects of curculigoside could be neutralized.

Conclusions

Curculigoside could induce the osteogenic differentiation of ADSCs and prevent bone loss in an OVX model through the PI3K/Akt signaling pathway.
One-stage posterior laminectomy with instrumented fusion and foraminotomy for cervical ossification of posterior longitudinal ligament with radiculopathy pain
Authors: Su Bao , Shen Jieliang , Luo Xiaoji , Quan Zhengxue , Jiang Dianming , Peng Xiaohua , Tang Ke
Published: April 2021

Objective

To explore the clinical efficacy of posterior LFF for cervical OPLL with radicular pain of upper limbs

Methods

Between January 2014 and January 2018, 48 OPLL patients with radicular pain symptoms of upper limbs who underwent a one-stage posterior laminectomy and instrumented fusion with/without foraminotomy were reviewed retrospectively and divided into two groups: LF group (laminectomy with instrumented fusion without foraminotomy) and LFF group (laminectomy with instrumented fusion and foraminotomy). Clinical data were assessed and compared between the two groups. The radicular pain of upper limbs and neck was measured using the visual analog scale (VAS). The neurological function was evaluated with the American Spinal Injury Association (ASIA) scale. Changes of sagittal alignment were investigated by postoperative plain x-ray or computed tomography (CT). Moreover, the decompression of the spinal cord was evaluated based on postoperative MRI.

Results

All the 48 patients were followed up for 24–42 months with an average follow-up time of 31.1±5.3 months. A total of 56 cervical intervertebral foramens were enlarged in 48 patients, including 40 cases (83.3%) with 1 intervertebral foramen enlargement and 8 cases (16.7%) with 2 intervertebral foramen enlargements. There were no significant differences in intraoperative blood loss, postoperative drainage amount, Japanese Orthopaedic Association (JOA) scores, JOA recovery rates, VAS scores for neck pain, and ASIA grade between two groups. The mean operative time was shorter in the LF group compared with the LFF group. The VAS score for arm pain was significantly lower while the surgical duration was longer in group B. No statistical difference was observed between the two groups in terms of C2–C7 SVA, cervical lordosis, focal angulation at the foraminotomy segment, and local spinal cord angle. Compared with the LF group, there was no segmental kyphosis or instability where the additional posterior foraminotomy was performed in the LFF group.

Conclusions

One-stage posterior LFF can achieve satisfied clinical efficacy in improving neurological function and relieving the radicular pain of the upper limbs for OPLL patients with radiculopathy symptoms.
Risk factors of postoperative delirium after cardiac surgery: a meta-analysis
Authors: Chen Haiyan , Mo Liang , Hu Hongjuan , Ou Yulan , Luo Juan
Published: April 2021

Background

Postoperative delirium is a frequent event after cardiac surgery. This meta-analysis aimed to identify relevant risk factors.

Method

In this meta-analysis, all original researches regarding patients undergoing mixed types of cardiac surgery (excluding transcatheter procedures) and postoperative delirium were evaluated for inclusion. On July 28th 2020, we searched PubMed, Embase, Web of Science and Scopus. Data about name of first author, year of publication, inclusion and exclusion criteria, research design, setting, method of delirium assessment, incidence of delirium, odds ratio (OR) and corresponding 95% confidence interval (CI) of risk factors, and other information relevant was collected. OR and 95% CI were used as metrics for summarized results. Random effects model was applied.

Results

Fourteen reports were included with a total sample size of 13,286. The incidence of delirium ranged from 4.1 to 54.9%. Eight risk factors were identified including aging, diabetes, preoperative depression, mild cognitive impairment, carotid artery stenosis, NYHA functional class III or IV, time of mechanical ventilation and length of intensive care unit stay.

Conclusion

In this study several risk factors associated with postoperative delirium after cardiac surgery were identified. Utilizing the information may allow us to identifying patients at high risk of developing postoperative delirium prior to delirium onset.
Current status of ctDNA in precision oncology for hepatocellular carcinoma
Authors: Li Yan , Zheng Yuanyuan , Wu Liwei , Li Jingjing , Ji Jie , Yu Qiang , Dai Weiqi , Feng Jiao , Wu Jianye , Guo Chuanyong
Published: April 2021

The conventional method used to obtain a tumor biopsy for hepatocellular carcinoma (HCC) is invasive and does not evaluate dynamic cancer progression or assess tumor heterogeneity. It is thus imperative to create a novel non-invasive diagnostic technique for improvement in cancer screening, diagnosis, treatment selection, response assessment, and predicting prognosis for HCC. Circulating tumor DNA (ctDNA) is a non-invasive liquid biopsy method that reveals cancer-specific genetic and epigenetic aberrations. Owing to the development of technology in next-generation sequencing and PCR-based assays, the detection and quantification of ctDNA have greatly improved. In this publication, we provide an overview of current technologies used to detect ctDNA, the ctDNA markers utilized, and recent advances regarding the multiple clinical applications in the field of precision medicine for HCC.
Childhood stunting and associated factors among irrigation and non-irrigation user northwest, Ethiopia: a comparative cross-sectional study
Authors: Sema Balew , Azage Muluken , Tirfie Mulat
Published: April 2021

Background

Stunting is a critical public health problem of developing countries like Ethiopia. Different interventions like irrigation activity have been carried out by the government of Ethiopia to improve the nutritional status of the community. However, there is scanty of data on childhood stunting and its associated factors between irrigation user and non-irrigation user.

Objective

To assess the magnitude of childhood stunting and its associated factors between irrigation and non-irrigation user in North Mecha District, Northwest Ethiopia.

Methods

A community-based comparative cross-sectional study design was employed from October to November 2019. A systematic sampling was used to draw mothers with children age 6–59 months (582 irrigated and 582 non- irrigated household users). Data were collected using questionnaire and anthropometric measurement tools. Multivariable logistic regression was used to identify the predictors of stunting. Adjusted odds ratios with 95% CI were used to determine the degree of association between independent and outcome variable. A-p-value < 0.05 was used as cutoff point to declare statistically significant variables with the outcome variable.

Results

The prevalence of childhood stunting (6–59 months) among irrigation users [32.8% at 95%CI [29.1%-36.7%]] was slightly lower than non-users [40.2% at 95%CI [[36.3%-44.2%]]]. However, the difference did not show significant variation. The odds of childhood stunting were higher among a child from a mother had no antenatal visit, a child whose age was between 12 and 47 months, a child from a mother who did not use water and soap always for washing hands, and a child who had fever.

Conclusion

The prevalence of childhood stunting was high and did not show significant variation between irrigation and non-irrigation users. A child from mother had no antenatal visit, whose age was between 12 and 47 months, a mother who did not use water and soap always for washing hands, and who had fever were factors associated with higher child stunting. Thus, the identified modifiable factors should be strengthened to reduce stunting.
Implications of cardiac markers in risk-stratification and management for COVID-19 patients
Authors: Li Pengping , Wu Wei , Zhang Tingting , Wang Ziyu , Li Jie , Zhu Mengyan , Liang Yuan , You Wenhua , Li Kening , Ding Rong , Huang Bin , Wu Lingxiang , Duan Weiwei , Han Yi , Li Xuesong , Tang Xin , Wang Xin , Shen Han , Wang Qianghu , Yan Hong , Xia Xinyi , Ji Yong , Chen Hongshan
Published: April 2021

Background

COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients.

Methods

A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression.

Results

Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50–68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4–4.8]).

Conclusions

COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.
Clinical effects of breast milk enema on meconium evacuation in premature infants: study protocol for a randomized controlled trial
Authors: Zheng Liqiang , Gai Li , Gao Jinyue , Kong Chaonan , Wang Yali , Sun Fangli , Liu Sitong , Yu Xinying , Yang Fan , Jiang Hong
Published: April 2021

Background

Delayed meconium evacuation is an important cause of intestinal dysfunction in preterm infants. There are many methods to induce defecation in preterm infants: however, the effects are controversial. Finding a new intervention method to promote meconium evacuation in premature infants is necessary. Therefore, in the proposed study, the effectiveness of breast milk enema on complete meconium evacuation and time to achieve full enteral feeding will be investigated in preterm infants.

Methods/design

The study is a randomized, open-label, parallel-group, and single-center clinical trial. A total of 294 preterm infants will be recruited and stratified based on gestational age. Then, the infants will be assigned in a randomized block design to the intervention and control groups with a 1:1 ratio. Preterm infants in the control and intervention groups will receive saline enema and breast milk enema, respectively. The primary outcomes will be the time to achieve complete meconium evacuation from birth and time to achieve full enteral feeding from birth in preterm infants. The secondary outcomes will include hospitalization days, body weight at discharge, duration of total parenteral nutrition, cholestasis, and adverse events.

Discussion

The results of this trial will determine whether breast milk enema shortens the time to complete meconium evacuation and the time to achieve full enteral feeding in extremely preterm and preterm infants. Furthermore, the study results may provide a new, safe, inexpensive, and easy-to-use intervention to effectively evacuate meconium in preterm infants.

Trial registration

ISRCTN Registry ISRCTN17847514. Registered on September 14, 2019
Synthesis of oxadiazole-2-oxide derivatives as potential drug candidates for schistosomiasis targeting SjTGR
Authors: Li Gongming , Guo Qingqing , Feng Chao , Chen Huan , Zhao Wenjiao , Li Shu , Hong Yang , Sun Dequn
Published: April 2021

Background

Schistosomiasis is a chronic parasitic disease that affects millions of people’s health worldwide. Because of the increasing drug resistance to praziquantel (PZQ), which is the primary drug for schistosomiasis, developing new drugs to treat schistosomiasis is crucial. Oxadiazole-2-oxides have been identified as potential anti-schistosomiasis reagents targeting thioredoxin glutathione reductase (TGR).

Methods

In this work, one of the oxadiazole-2-oxides derivatives furoxan was used as the lead compound to exploit a series of novel furoxan derivatives for studying inhibitory activity against both recombinant Schistosoma japonicum TGR containing selenium (rSjTGR-Sec) and soluble worm antigen protein (SWAP) containing wild-type Schistosoma japonicum TGR (wtSjTGR), in order to develop a new leading compound for schistosomiasis. Thirty-nine novel derivatives were prepared to test their activity toward both enzymes. The docking method was used to detect the binding site between the active molecule and SjTGR. The structure–activity relationship (SAR) of these novel furoxan derivatives was preliminarily analyzed.

Results

It was found that several new derivatives, including compounds 6a–6d, 9ab, 9bd and 9be, demonstrated greater activity toward rSjTGR-Sec or SWAP containing wtSjTGR than did furoxan. Interestingly, all intermediates bearing hydroxy (6a–6d) showed excellent inhibitory activity against both enzymes. In particular, compound 6d with trifluoromethyl on a pyridine ring was found to have much higher inhibition toward both rSjTGR-Sec (half-maximal inhibitory concentration, IC50,7.5nM) and SWAP containing wtSjTGR (IC50 55.8nM) than furoxan. Additionally, the docking method identified the possible matching sites between 6d and Schistosoma japonicum TGR (SjTGR), which theoretically lends support to the inhibitory activity of 6d.

Conclusion

The data obtained herein showed that 6d with trifluoromethyl on a pyridine ring could be a valuable leading compound for further study.

Graphical Abstract