bluuebunny/crossref_metadata_2025 huggingface dataset:
Bereavement interventions to support informal caregivers in the intensive care unit: a systematic review
Authors: Moss Stephana J. , Wollny Krista , Poulin Therese G. , Cook Deborah J. , Stelfox Henry T. , Ordons Amanda Roze des , Fiest Kirsten M.
Published: May 2021

Background

Informal caregivers of critically ill patients in intensive care unit (ICUs) experience negative psychological sequelae that worsen after death. We synthesized outcomes reported from ICU bereavement interventions intended to improve informal caregivers’ ability to cope with grief.

Data sources

MEDLINE, EMBASE, CINAHL and PsycINFO from inception to October 2020.

Study selection

Randomized controlled trials (RCTs) of bereavement interventions to support informal caregivers of adult patients who died in ICU.

Data extraction

Two reviewers independently extracted data in duplicate. Narrative synthesis was conducted.

Data synthesis

Bereavement interventions were categorized according to the UK National Institute for Health and Clinical Excellence three-tiered model of bereavement support according to the level of need: (1) Universal information provided to all those bereaved; (2) Selected or targeted non-specialist support provided to those who are at-risk of developing complex needs; and/or (3) Professional specialist interventions provided to those with a high level of complex needs. Outcome measures were synthesized according to core outcomes established for evaluating bereavement support for adults who have lost other adults to illness.

Results

Three studies of ICU bereavement interventions from 31 ICUs across 26 hospitals were included. One trial examining the effect of family presence at brain death assessment integrated all three categories of support but did not report significant improvement in emotional or psychological distress. Two other trials assessed a condolence letter intervention, which did not decrease grief symptoms and may have increased symptoms of depression and post-traumatic stress disorder, and a storytelling intervention that found no significant improvements in anxiety, depression, post-traumatic stress, or complicated grief. Four of nine core bereavement outcomes were not assessed anytime in follow-up.

Conclusions

Currently available trial evidence is sparse and does not support the use of bereavement interventions for informal caregivers of critically ill patients who die in the ICU.
Spatial variability in factors influencing maternal health service use in Jimma Zone, Ethiopia: a geographically-weighted regression analysis
Authors: Kurji Jaameeta , Thickstun Charles , Bulcha Gebeyehu , Taljaard Monica , Li Ziqi , Kulkarni Manisha A.
Published: May 2021

Background

Persisting within-country disparities in maternal health service access are significant barriers to attaining the Sustainable Development Goals aimed at reducing inequalities and ensuring good health for all. Sub-national decision-makers mandated to deliver health services play a central role in advancing equity but require appropriate evidence to craft effective responses. We use spatial analyses to identify locally-relevant barriers to access using sub-national data from rural areas in Jimma Zone, Ethiopia.

Methods

Cross-sectional data from 3727 households, in three districts, collected at baseline in a cluster randomized controlled trial were analysed using geographically-weighted regressions. These models help to quantify associations within women’s proximal contexts by generating local parameter estimates. Data subsets, representing an empirically-identified scale for neighbourhood, were used. Local associations between outcomes (antenatal, delivery, and postnatal care use) and potential explanatory factors at individual-level (ex: health information source), interpersonal-level (ex: companion support availability) and health service-levels (ex: nearby health facility type) were modelled. Statistically significant local odds ratios were mapped to demonstrate how relevance and magnitude of associations between various explanatory factors and service outcomes change depending on locality.

Results

Significant spatial variability in relationships between all services and their explanatory factors (p < 0.001) was detected, apart from the association between delivery care and women’s decision-making involvement (p = 0.124). Local models helped to pinpoint factors, such as danger sign awareness, that were relevant for some localities but not others. Among factors with more widespread influence, such as that of prior service use, variation in estimate magnitudes between localities was uncovered. Prominence of factors also differed between services; companion support, for example, had wider influence for delivery than postnatal care. No significant local associations with postnatal care use were detected for some factors, including wealth and decision involvement, at the selected neighbourhood scale.

Conclusions

Spatial variability in service use associations means that the relative importance of explanatory factors changes with locality. These differences have important implications for the design of equity-oriented and responsive health systems. Reductions in within-country disparities are also unlikely if uniform solutions are applied to heterogeneous contexts. Multi-scale models, accommodating factor-specific neighbourhood scaling, may help to improve estimated local associations.
Identification of four insertion sites for foreign genes in a pseudorabies virus vector
Authors: Zhang Chuanjian , Guo Shiqi , Guo Rongli , Chen Saisai , Zheng Yating , Xu Mengwei , Wang Zhisheng , Liu Yamei , Wang Jichun
Published: May 2021

Background

Pseudorabies virus (PRV) is a preferred vector for recombinant vaccine construction. Previously, we generated a TK&gE-deleted PRV (PRVΔTK&gE−AH02) based on a virulent PRV AH02LA strain. It was shown to be safe for 1-day-old piglets with maternal PRV antibodies and 4 ~ 5 week-old PRV antibody negative piglets and provide rapid and 100 % protection in weaned pigs against lethal challenge with the PRV variant strain. It suggests that PRVTK&gE−AH02 may be a promising live vaccine vector for construction of recombinant vaccine in pigs. However, insertion site, as a main factor, may affect foreign gene expression.

Results

In this study, we constructed four recombinant PRV-S bacterial artificial chromosomes (BACs) carrying the same spike (S) expression cassette of a variant porcine epidemic diarrhea virus strain in different noncoding regions (UL11-10, UL35-36, UL46-27 or US2-1) from AH02LA BAC with TK, gE and gI deletion. The successful expression of S gene (UL11-10, UL35-36 and UL46-27) in recombinant viruses was confirmed by virus rescue, PCR, real-time PCR and indirect immunofluorescence. We observed higher S gene mRNA expression level in swine testicular cells infected with PRV-S(UL11-10)ΔTK/gE and PRV-S(UL35-36)ΔTK/gE compared to that of PRV-S(UL46-27)ΔTK/gE at 6 h post infection (P < 0.05). Moreover, at 12 h post infection, cells infected with PRV-S(UL11-10)ΔTK/gE exhibited higher S gene mRNA expression than those infected with PRV-S(UL35-36)ΔTK/gE (P = 0.097) and PRV-S(UL46-27)ΔTK/gE (P < 0.05). Recovered vectored mutant PRV-S (UL11-10, UL35-36 and UL46-27) exhibited similar growth kinetics to the parental virus (PRVΔTK&gE−AH02).

Conclusions

This study focuses on identification of suitable sites for insertion of foreign genes in PRV genome, which laids a foundation for future development of recombinant PRV vaccines.
Implementing radical cure diagnostics for malaria: user perspectives on G6PD testing in Bangladesh
Authors: Engel Nora , Ghergu Cristian , Matin Mohammad Abdul , Kibria Mohammad Golam , Thriemer Kamala , Price Ric N. , Ding Xavier C. , Howes Rosalind E. , Ley Benedikt , Incardona Sandra , Alam Mohammad Shafiul
Published: May 2021

Background

The radical cure of Plasmodium vivax requires treatment with an 8-aminoquinoline drug, such as primaquine and tafenoquine, to eradicate liver hypnozoite stages, which can reactivate to cause relapsing infections. Safe treatment regimens require prior screening of patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency to avoid potential life-threatening drug induced haemolysis. Testing is rarely available in malaria endemic countries, but will be needed to support routine use of radical cure. This study investigates end-user perspectives in Bangladesh on the introduction of a quantitative G6PD test (SD Biosensor STANDARD™ G6PD analyser) to support malaria elimination.

Methods

The perspectives of users on the SD Biosensor test were analysed using semi-structured interviews and focus group discussions with health care providers and malaria programme officers in Bangladesh. Key emerging themes regarding the feasibility of introducing this test into routine practice, including perceived barriers, were analysed.

Results

In total 63 participants were interviewed. Participants emphasized the life-saving potential of the biosensor, but raised concerns including the impact of limited staff time, high workload and some technical aspects of the device. Participants highlighted that there are both too few and too many P. vivax patients to implement G6PD testing owing to challenges of funding, workload and complex testing infrastructure. Implementing the biosensor would require flexibility and improvisation to deal with remote sites, overcoming a low index of suspicion and mutual interplay of declining patient numbers and reluctance to test. This approach would generate new forms of evidence to justify introduction in policy and carefully consider questions of deployment given declining patient numbers.

Conclusions

The results of the study show that, in an elimination context, the importance of malaria needs to be maintained for both policy makers and the affected communities, in this case by ensuring P. vivax, PQ treatment, and G6PD deficiency remain visible. Availability of new technologies, such as the biosensor, will fuel ongoing debates about priorities for allocating resources that must be adapted to a constantly evolving target. Technical and logistical concerns regarding the biosensor should be addressed by future product designs, adequate training, strengthened supply chains, and careful planning of communication, advocacy and staff interactions at all health system levels.
ATF5 and HIF1α cooperatively activate HIF1 signaling pathway in esophageal cancer
Authors: He Feng , Xiao Hang , Cai Yixin , Zhang Ni
Published: May 2021

Background

Esophageal cancer (ESCA) is one of the most common cancers worldwide and has a very poor prognosis. Hypoxia-inducible factor 1 (HIF1) signaling pathway plays a critical role in tumorigenesis and is therefore considered a potential therapeutic target in the treatment of many cancers. Activating transcription factor 5 (ATF5) facilitates the expression of various genes and has been extensively studied for its potential role in cancer treatment.

Methods

The expression level of ATF5 in clinic sample was detected by quantitative real time PCR and immunohistochemistry. ATF5 biological function was investigated by western blot, cell cycle analysis, cell viability assay, luciferase reporter assays, colony formation assay, transwell assay, wound healing assay, tube formation assay, and ELISA assay. CHIP and Re-CHIP assay, GST-pulldown, and RNA-sequencing were used to study the cross-talks between ATF5 and HIF1 complex. Mouse xenograft study was utilized to study the correlation of ATF5 and tumor growth in vivo. Student’s t-test or Chi-square test was used for statistical analysis.

Results

Here, we first found ATF5 was dramatically upregulated in ESCA cancer and related with poor survival time. Next, we found that the expression level of ATF5 had a positive relationship with the proliferation, migration, and invasion ability of ESCA cells. Besides, we innovatively found that ATF5 functions as a novel coactivator in HIF1 transcription complex by binding to HIF1α. Further, we demonstrated that silencing ATF5 phenocopies HIF1α knockdown in tumorigenic properties in vitro and inhibited ESCA tumor angiogenesis and proliferation in vivo.

Conclusion

Herein, we found ATF5 as a novel component of the HIF1 transcription complex. The findings of the present study may provide new insights into the development of a novel and more efficient therapeutic strategy against ESCA.
The culture microenvironment of juvenile idiopathic arthritis synovial fibroblasts is favorable for endochondral bone formation through BMP4 and repressed by chondrocytes
Authors: Simonds Megan M. , Schlefman Amanda R. , McCahan Suzanne M. , Sullivan Kathleen E. , Rose Carlos D. , Brescia Anne Marie C.
Published: May 2021

Background

We examined influences of conditioned media from chondrocytes (Ch) on juvenile idiopathic arthritis synovial fibroblasts (JFLS) and potential for JFLS to undergo endochondral bone formation (EBF).

Methods

Primary cells from three control fibroblast-like synoviocytes (CFLS) and three JFLS were cultured in Ch-conditioned media and compared with untreated fibroblast-like synoviocytes (FLS). RNA was analyzed by ClariomS microarray. FLS cells cultured in conditioned media were exposed to either TGFBR1 inhibitor LY3200882 or exogenous BMP4 and compared with FLS cultured in conditioned media from Ch (JFLS-Ch). Media supernatants were analyzed by ELISA.

Results

In culture, JFLS downregulate BMP2 and its receptor BMPR1a while upregulating BMP antagonists (NOG and CHRD) and express genes (MMP9, PCNA, MMP12) and proteins (COL2, COLX, COMP) associated with chondrocytes. Important TGFβ superfamily member gene expression (TGFBI, MMP9, COL1A1, SOX6, and MMP2) is downregulated when JFLS are cultured in Ch-conditioned media. COL2, COLX and COMP protein expression decreases in JFLS-Ch. BMP antagonist protein (NOG, CHRD, GREM, and FST) secretion is significantly increased in JFLS-Ch. Protein phosphorylation increases in JFLS-Ch exposed to exogenous BMP4, and chondrocyte-like phenotype is restored in BMP4 presence, evidenced by increased secretion of COL2 and COLX. Inhibition of TGFBR1 in JFLS-Ch results in overexpression of COL2.

Conclusions

JFLS are chondrocyte-like, and Ch-conditioned media can abrogate this phenotype. The addition of exogenous BMP4 causes JFLS-Ch to restore this chondrocyte-like phenotype, suggesting that JFLS create a microenvironment favorable for endochondral bone formation, thereby contributing to joint growth disturbances in juvenile idiopathic arthritis.
Association between depression and HIV treatment outcomes in a US military population with HIV infection
Authors: Carney Brandon , Daniels Colton , Xu Xiaohe , Sunil Thankam , Ganesan Anuradha , Blaylock Jason M. , Kronmann Karl C. , Schofield Christina , Lalani Tahaniyat , Agan Brian , Okulicz Jason F.
Published: May 2021

Background

Depression is common among HIV-infected individuals and may contribute to suboptimal adherence to antiretroviral therapy (ART) and subsequent inability to attain viral load (VL) suppression. We evaluated associations between depression, self-reported adherence, and longitudinal HIV treatment outcomes in US Military HIV Natural History Study (NHS) participants with and without depression.

Methods

Male NHS participants with available ICD-9 data for mental health diagnoses, Center for Epidemiological Studies Depression (CES-D) measures, and self-reported adherence (SRA) were included. ART use was defined as ART initiation between 2006 and 2010, with follow-up through 2015. SRA was defined as taking 95% of ART doses and continuous ART was defined as longitudinal ART use with gaps  < 30 days. Continuous VL suppression was defined as maintaining VLs  < 200 c/mL on ART. To analyse the association between depression and HIV treatment outcomes, latent class analysis was used to create classes of depression trajectories: low depression (LD), recent onset depression (ROD) and high Depression (HD).

Results

Participants had a mean age of 32 (± 8.3) years at HIV diagnosis, and similar proportions were Caucasian (44.3%) or African American (40.8%). Overall, older participants at HIV diagnosis had greater odds of having 95% self-reported adherence (OR 1.06, 95% CI 1.02–1.12), and African Americans had lower odds (OR 0.41, 95% CI 0.22–0.76) compared to Caucasians (OR 1.49, 95% CI 0.52–4.28). However, there was no difference in SRA by depression trajectory. Participants with HD had an increased odds of taking ART continuously (OR 1.75, 95% CI 0.99–3.09), and those with ROD had significantly higher odds of virologic failure (OR 0.58, 95% CI 0.38–0.91).

Conclusions

Although there was no observed association between depression and SRA, participants with ROD had lower odds of attaining the HIV treatment goal of VL suppression. Continued efforts to identify and aggressively manage mental health disorders is important to success along the HIV care continuum.
Correction to: Restoration of bilateral motor coordination from preserved agonist-antagonist coupling in amputation musculature
Authors: Shu Tony , Huang Shan Shan , Shallal Christopher , Herr Hugh M.
Published: May 2021

An amendment to this paper has been published and can be accessed via the original article.
Involvement of mental health professionals in the treatment of tuberous sclerosis complex–associated neuropsychiatric disorders (TAND): results of a multinational European electronic survey
Authors: Waltereit Robert , Beaure d’Augères Guillaume , Jancic Jasna , Kingswood John Chris , Koleva Maya , Marques Ruben , Villanueva Vicente , Auvin Stéphane
Published: May 2021

Background

Tuberous sclerosis complex (TSC) is a rare, genetic, multisystem disorder characterized by the growth of hamartomas in several organs, including the brain, kidneys, heart, eyes, and lungs. Even though over 90% of patients will have some form of TSC-associated neuropsychiatric disorder (TAND), there is an apparent lack of involvement of mental health professionals (MHPs) in the care of patients with TSC. The aim of this study was to determine the current level of TAND awareness in the TSC community and to identify possible barriers to effective multidisciplinary collaboration between MHPs and other healthcare providers (HCPs) in TAND management.

Methods

An electronic survey on current TSC and TAND management was conducted, targeting TSC caregivers/families, psychiatrists, neurologists, TSC specialists, and primary care physicians.

Results

The invitation to participate in the survey was emailed to 659 HCPs and was disseminated through social media channels of patient advocacy groups. The survey was open for 4 months, with 359 responses collected. The majority of participants were TSC caregivers/families (73.3% of all responses). Of the 96 HCPs who participated, most were neurologists (61.5%) or TSC specialists (28.1%). Only 6 psychiatrists and 4 primary care physicians participated. Approximately half of patients have never had a neuropsychiatric assessment, and it was their caregivers/families who initiated the discussion of TAND with their providers. Almost 70% of TSC caregivers/families believed that psychiatric treatment could improve their quality of life. However, 54% of patients had difficulty obtaining psychiatric assessment. In turn, only 21% of HCPs believed that psychiatric therapy would help and 74% were concerned that their patients would be stigmatized by psychiatric referral.

Conclusions

This study focused on European healthcare systems suggests that current care for mental health issues in patients with TSC is inadequate, despite guideline recommendations for regular neuropsychiatric assessments. This appears to be due to a combination of gaps in diagnosis and surveillance, low frequency of psychiatric referrals, insufficient resources, and stigmatization of mental healthcare. There is a pressing need for further initiatives to study and address the mechanisms underlying the mental health treatment gap. The importance of MHP support must be recognized to optimize TSC management.
Subcutaneous vitamin B12 administration using a portable infusion pump in cobalamin-related remethylation disorders: a gentle and easy to use alternative to intramuscular injections
Authors: Lotz-Havla Amelie S. , Weiß Katharina J. , Schiergens Katharina A. , Brunet Theresa , Kohlhase Jürgen , Regenauer-Vandewiele Stephanie , Maier Esther M.
Published: May 2021

Background

Cobalamin (cbl)-related remethylation disorders are a heterogeneous group of inherited disorders comprising the remethylation of homocysteine to methionine and affecting multiple organ systems, most prominently the nervous system and the bone marrow. To date, the parenteral, generally intramuscular, lifelong administration of hydroxycobalamin (OHCbl) is the mainstay of therapy in these disorders. The dosage and frequency of OHCbl is titrated in each patient to the minimum effective dose in order to account for the painful injections. This may result in undertreatment, a possible risk factor for disease progression and disease-related complications.

Results

We describe parenteral administration of OHCbl using a subcutaneous catheter together with a portable infusion pump in a home therapy setting in four pediatric patients with remethylation disorders, two patients with cblC, one patient with cblG, and one patient with cblE deficiency, in whom intramuscular injections were not or no longer feasible. The placement of the subcutaneous catheters and handling of the infusion pump were readily accomplished and well accepted by the patients and their families. No adverse events occurred. The use of a small, portable syringe driver pump allowed for a most flexible administration of OHCbl in everyday life. The concentrations of total homocysteine levels were determined at regular patient visits and remained within the therapeutic target range. This approach allowed for the continuation of OHCbl therapy or the adjustment of therapy required to improve metabolic control in our patients.

Conclusions

Subcutaneous infusion using a subcutaneous catheter system and a portable pump for OHCbl administration in combined and isolated remethylation disorders is safe, acceptable, and effective. It decreases disease burden in preventing frequent single injections and providing patient independence. Thus, it may promote long-term adherence to therapy in patients and parents.
Effectiveness and cost-effectiveness of integrating the management of depression into routine HIV Care in Uganda (the HIV + D trial): A protocol for a cluster-randomised trial
Authors: Kinyanda Eugene , Kyohangirwe Leticia , Mpango Richard S. , Tusiime Christine , Ssebunnya Joshua , Katumba Kenneth , Tenywa Patrick , Mugisha James , Taasi Geoffrey , Sentongo Hafsa , Akena Dickens , Laurence Yoko , Muhwezi Wilson , Weiss Helen A. , Neuman Melissa , Greco Giulia , Knizek Birthe , Levin Jonathan , Kaleebu Pontiano , Araya Ricardo , Ssembajjwe Wilber , Patel Vikram
Published: May 2021

Background

An estimated 8–30 % of people living with HIV (PLWH) have depressive disorders (DD) in sub-Saharan Africa. Of these, the majority are untreated in most of HIV care services. There is evidence from low- and middle- income countries of the effectiveness of both psychological treatments and antidepressant medication for the treatment of DD among PLWH, but no evidence on how these can be integrated into routine HIV care. This protocol describes a cluster-randomised trial to evaluate the effectiveness and cost-effectiveness of the HIV + D model for the integration of a collaborative stepped care intervention for DD into routine HIV care, which we have developed and piloted in Uganda.

Methods

Forty public health care facilities that provide HIV care in Kalungu, Masaka and Wakiso Districts will be randomly selected to participate in the trial. Each facility will recruit 10–30 eligible PLWH with DD and the total sample size will be 1200. The clusters will be randomised 1:1 to receive Enhanced Usual Care alone (EUC, i.e. HIV clinicians trained in Mental Health Gap Action Programme including guidelines on when and where to refer patients for psychiatric care) or EUC plus HIV + D (psychoeducation, Behavioural Activation, antidepressant medication and referral to a supervising mental health worker, delivered in a collaborative care stepwise approach). Eligibility criteria are PLWH attending the clinic, aged ≥ 18 years who screen positive on a depression screening questionnaire (Patient Health Questionnaire, PHQ-9 ≥ 10). The primary outcome is the mean depressive disorder symptom severity scores (assessed using the PHQ-9) at 3 months’ post-randomisation, with secondary mental health, disability, HIV and economic outcomes measured at 3 and 12 months. The cost-effectiveness of EUC with HIV + D will be assessed from both the health system and the societal perspectives by collecting health system, patient and productivity costs and mean DD severity scores at 3 months, additional to health and non-health related quality of life measures (EQ-5D-5 L and OxCAP-MH).

Discussion

The study findings will inform policy makers and practitioners on the cost-effectiveness of a stepped care approach to integrate depression management in routine care for PLWH in low-resource settings.

Trial registration: ISRCTN, ISRCTN86760765. Registered 07 September 2017, 10.1186/ISRCTN86760765.
Immunotherapies targeting stimulatory pathways and beyond
Authors: Marin-Acevedo Julian A. , Kimbrough ErinMarie O. , Manochakian Rami , Zhao Yujie , Lou Yanyan
Published: May 2021

Co-stimulatory and co-inhibitory molecules play a critical role in T cell function. Tumor cells escape immune surveillance by promoting immunosuppression. Immunotherapy targeting inhibitory molecules like anti-CTLA-4 and anti-PD-1/PD-L1 were developed to overcome these immunosuppressive effects. These agents have demonstrated remarkable, durable responses in a small subset of patients. The other mechanisms for enhancing anti-tumor activities are to target the stimulatory pathways that are expressed on T cells or other immune cells. In this review, we summarize current phase I/II clinical trials evaluating novel immunotherapies targeting stimulatory pathways and outline their advantages, limitations, and future directions.
MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma
Authors: Yang Mengkai , Zhang Tao , Zhang Yangfeng , Ma Xiaojun , Han Jing , Zeng Ke , Jiang Yafei , Wang Zongyi , Wang Zhuoying , Xu Jing , Hua Yingqi , Cai Zhengdong , Sun Wei
Published: May 2021

Background

Osteosarcoma (OS) is the most common primary bone cancer in adolescents and lung metastasis is the leading cause of death in patients with OS. However, the molecular mechanisms that promote OS growth and metastasis remain unknown.

Methods

We investigated the expression of myosin light chain kinase family members between metastasis and non-metastasis patients in the TARGET database and ensured that only myosin light chain kinase family member 4 (MYLK4) had higher expression in metastatic osteosarcoma patients. Then we confirmed the results by immunohistochemistry (IHC) and Western blotting (WB) of OS tissues. The effect of MYLK4 on the metastasis and proliferation of OS cells was investigated by wound healing, Transwell and colony-formation assays. Mass spectrum analysis was used to ensure the new binding protein of MYLK4. Tissue microarrays analysis was used to show the correlation between MYLK4 and pEGFR (Y1068). A series of in vivo experiments were conducted to reveal the mechanisms by which MYLK4 modulated the metastasis and proliferation of OS.

Results

Myosin Light Chain Kinase Family Member 4 (MYLK4) was significantly upregulated in metastatic human OS tissues. Growth and metastasis of OS could be accelerated by MYLK4 overexpression, whereas silencing MYLK4 expression resulted in decreased cell growth and metastasis. Mechanistically, mass spectrum analysis showed that MYLK4 interacted with the epidermal growth factor receptor (EGFR) in osteosarcoma cells and promoted growth and metastasis via the EGFR signaling pathway. Tissue microarrays analysis also showed that MYLK4 expression had a positive correlation with the expression of pEGFR (Y1068). Moreover, the EGFR inhibitor gefitinib could partially reverse the effect of cell proliferation and metastasis caused by MYLK4 overexpression. Importantly, the combination of MYLK4 and EGFR inhibitors had synergistic effects on growth and metastasis of OS in vitro and in vivo.

Conclusion

Our results indicate that MYLK4 promotes OS growth and metastasis by activating the EGFR signaling pathway and can be a novel therapeutic target for the treatment of OS patients.
IDSM ChemWebRDF: SPARQLing small-molecule datasets
Authors: Galgonek Jakub , Vondrášek Jiří
Published: May 2021

The Resource Description Framework (RDF), together with well-defined ontologies, significantly increases data interoperability and usability. The SPARQL query language was introduced to retrieve requested RDF data and to explore links between them. Among other useful features, SPARQL supports federated queries that combine multiple independent data source endpoints. This allows users to obtain insights that are not possible using only a single data source. Owing to all of these useful features, many biological and chemical databases present their data in RDF, and support SPARQL querying. In our project, we primary focused on PubChem, ChEMBL and ChEBI small-molecule datasets. These datasets are already being exported to RDF by their creators. However, none of them has an official and currently supported SPARQL endpoint. This omission makes it difficult to construct complex or federated queries that could access all of the datasets, thus underutilising the main advantage of the availability of RDF data. Our goal is to address this gap by integrating the datasets into one database called the Integrated Database of Small Molecules (IDSM) that will be accessible through a SPARQL endpoint. Beyond that, we will also focus on increasing mutual interoperability of the datasets. To realise the endpoint, we decided to implement an in-house developed SPARQL engine based on the PostgreSQL relational database for data storage. In our approach, data are stored in the traditional relational form, and the SPARQL engine translates incoming SPARQL queries into equivalent SQL queries. An important feature of the engine is that it optimises the resulting SQL queries. Together with optimisations performed by PostgreSQL, this allows efficient evaluations of SPARQL queries. The endpoint provides not only querying in the dataset, but also the compound substructure and similarity search supported by our Sachem project. Although the endpoint is accessible from an internet browser, it is mainly intended to be used for programmatic access by other services, for example as a part of federated queries. For regular users, we offer a rich web application called ChemWebRDF using the endpoint. The application is publicly available at https://idsm.elixir-czech.cz/chemweb/.
The YAP/HIF-1α/miR-182/EGR2 axis is implicated in asthma severity through the control of Th17 cell differentiation
Authors: Zhou Jing , Zhang Ning , Zhang Wei , Lu Caiju , Xu Fei
Published: May 2021

Background

Asthma is a heterogeneous chronic inflammatory disease of the airway, involving reversible airflow limitation and airway remodeling. T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. However, there is limited understanding of the signaling pathways controlling Th17 cell differentiation in asthma. The aim of this study was to investigate if the Yes-associated protein (YAP)/hypoxia inducible factor-1α (HIF-1α)/microRNA-182 (miR-182)/early growth response 2 (EGR2) axis is involved in mediating Th17 cell differentiation and disease severity in asthma.

Methods

The study included 29 pediatric patients with asthma, 22 healthy volunteers, ovalbumin-induced murine asthma models, and mouse naive CD4+T cells. The subpopulation of Th17 cells was examined by flow cytometry. The levels of interleukin-17A were determined by enzyme linked immunosorbent assay. Chromatin immunoprecipitation-quantitative polymerase chain reaction assays and dual-luciferase reporter gene assays were performed to examine interactions between HIF-1α and miR-182, and between miR-182 and EGR2.

Results

YAP, HIF-1α, and miR-182 were upregulated but EGR2 was downregulated in human and mouse peripheral blood mononuclear cells from the asthma group. Abundant expression of YAP and HIF-1α promoted miR-182 expression and then inhibited EGR2, a target of miR-182, thus enhancing Th17 differentiation and deteriorating asthma and lipid metabolism dysfunction. In addition, in vivo overexpression of EGR2 countered the promoting effect of the YAP/HIF-1α/miR-182 axis on asthma and lipid metabolism dysfunction.

Conclusion

These results indicate that activation of the YAP/HIF-1α/miR-182/EGR2 axis may promote Th17 cell differentiation, exacerbate asthma development, and aggravate lipid metabolism dysfunction, thus suggesting a potential therapeutic target for asthma.
Non-frontal facial expression recognition based on salient facial patches
Authors: Jiang Bin , Zhang Qiuwen , Li Zuhe , Wu Qinggang , Zhang Huanlong
Published: May 2021

Methods using salient facial patches (SFPs) play a significant role in research on facial expression recognition. However, most SFP methods use only frontal face images or videos for recognition, and they do not consider head position variations. We contend that SFP can be an effective approach for recognizing facial expressions under different head rotations. Accordingly, we propose an algorithm, called profile salient facial patches (PSFP), to achieve this objective. First, to detect facial landmarks and estimate head poses from profile face images, a tree-structured part model is used for pose-free landmark localization. Second, to obtain the salient facial patches from profile face images, the facial patches are selected using the detected facial landmarks while avoiding their overlap or the transcending of the actual face range. To analyze the PSFP recognition performance, three classical approaches for local feature extraction, specifically the histogram of oriented gradients (HOG), local binary pattern, and Gabor, were applied to extract profile facial expression features. Experimental results on the Radboud Faces Database show that PSFP with HOG features can achieve higher accuracies under most head rotations.
Determinants of adherence to COVID-19 measures among the Belgian population: an application of the protection motivation theory
Authors: van Loenhout Joris Adriaan Frank , Vanderplanken Kirsten , Scheen Bénédicte , Van den Broucke Stephan , Aujoulat Isabelle
Published: May 2021

Background

Since the start of the COVID-19 outbreak, the Belgian government has implemented various infection prevention and control measures. This study assessed the extent to which the general population in Belgium adhered to these measures, and which determinants were associated with adherence.

Methods

We undertook an internet survey among a sample of the Belgian population, representative for sex, age, socio-economic status and province. The questionnaire included various demographic, socio-economic and health-related questions, and also drew upon the Protection Motivation Theory as a theoretical framework to measure levels of perceived severity, vulnerability, perceived usefulness of the measures (response efficacy), perceived personal capacity to adhere (self-efficacy), and past and future adherence. Data were collected in Dutch and French, the main languages of Belgium.

Results

Our study was carried out in September 2020, and the number of respondents was 2008. On average, respondents provided high scores for each of the measures in place in September in terms of response efficacy (range of 3.54–4.32 on 1 to 5 Likert-scale), self-efficacy (range of 3.00–4.00), past adherence (4.00–4.68) and future adherence (3.99–4.61). The measure that overall received the highest scores was wearing a face mask in public spaces, while ‘the social bubble of 5’ generally received the lowest scores. There was a statistically significant relationship between response efficacy and self-efficacy on the one hand and (past and future) adherence on the other hand, in a multivariate model corrected for confounders. Vulnerability and severity did not show statistical significance.

Conclusion

Risk communication regarding COVID-19 should place a stronger emphasis on helping people understand why implemented measures are useful and how they can be put into practice, more than on increasing fear appeals.
Housing, opportunities, motivation and engagement (HOME) for homeless youth at-risk for opioid use disorder: study protocol for a randomized controlled trial
Authors: Slesnick Natasha , Chavez Laura , Bunger Alicia , Famelia Ruri , Ford Jodi , Feng Xin , Higgins Sarah , Holowacz Eugene , Jaderlund Soren , Luthy Ellison , Mallory Allen , Martin Jared , Walsh Laura , Yilmazer Tansel , Kelleher Kelly
Published: May 2021

Background

Homeless youth experience high rates of substance use disorders, exposures to violence, mental and physical health conditions, and mortality. They have been particularly affected by the opioid crisis. However, no study to date has used a randomized controlled design to test preventive interventions of opioid and other drug use among this vulnerable population. Resolution of youth homelessness through housing and supportive services including prevention services, often referred to as “Housing First,” has great potential to reduce the likelihood for the development of an opioid use disorder as well as other problem behaviors associated with living on the streets. Housing First has been tested through randomized trials among homeless adults with mental health and substance use disorders, but has not been empirically tested for opioid prevention among homeless youth.

Methods

Homeless youth will be recruited from a drop-in shelter site frequented by disconnected youth; they will be screened for eligibility, including current homelessness, age 18–24 years, and not currently meeting criteria for opioid use disorder (OUD). In a controlled trial, 240 youth will then be randomized to one of two conditions, (1) housing + opioid and related risk prevention services, or (2) opioid and related risk prevention services alone. This project utilizes existing efficacious models of prevention to address opioid-related risks, including motivational interviewing, strengths-based outreach and advocacy, and an HIV risk preventive intervention. Follow-up will be conducted at 3, 6, 9 and 12-months post-baseline. The economic cost of each intervention will be determined to support implementation decisions with other providers and their funders.

Discussion

This study will provide essential information for researchers and providers on the efficacy of housing + opioid and related risk prevention services in an RCT for effects on opioid use and mechanisms underlying change. Because youth experiencing homelessness are at increased risk for a variety of adverse outcomes, the proposed intervention may produce substantial health care benefits to the youths and society at large.

Trial registrationClinicalTrials.gov, NCT04135703, Registered October 13, 2019,https://clinicaltrials.gov/ct2/show/NCT04135703?term=NCT04135703&draw=2&rank=1#contacts
Patient outcomes and experience of a task-shared screening and brief intervention service for problem substance use in South African emergency centres: a mixed methods study
Authors: van der Westhuizen Claire , Malan Megan , Naledi Tracey , Roelofse Marinda , Myers Bronwyn , Stein Dan J. , Lahri Sa’ad , Sorsdahl Katherine
Published: May 2021

Background

Screening, brief intervention and referral to treatment (SBIRT) programmes have resulted in generally positive outcomes in healthcare settings, particularly for problem alcohol use, yet implementation is hampered by barriers such as concerns regarding the burden on healthcare professionals. In low-resourced settings, task-sharing approaches can reduce this burden by using non-professional healthcare workers, yet data are scarce regarding the outcomes and acceptability to patients within a SBIRT service. This study aims to evaluate patient-reported outcomes, patient acceptability, perceived benefits and recommendations for improving a task-shared SBIRT service in South African emergency centres (ECs).

Methods

This mixed methods study incorporates quantitative substance use screening and patient satisfaction data collected routinely within the service at three hospitals, and qualitative semi-structured interviews with 18 EC patient beneficiaries of the programme exploring acceptability and perceived benefits of the programme, as well as recommendations to improve the service. Approximately three months after the acute EC visit, a sub-sample of patients were followed up telephonically to assess patient-reported satisfaction and substance use outcomes.

Results

Of the 4847 patients eligible for the brief intervention, 3707 patients (76%) used alcohol as their primary substance and 794 (16%) used cannabis. At follow-up (n = 273), significant reductions in substance use frequency and severity were noted and over 95% of patients were satisfied with the service. In the semi-structured interviews, participants identified the non-judgemental caring approach of the counsellors, and the screening and psychoeducation components of the intervention as being the most valuable, motivating them to decrease substance use and make other positive lifestyle changes. Study participants made recommendations to include group sessions, market the programme in communities and extend the programme’s reach to include a broader age group and a variety of settings.

Conclusions

This task-shared SBIRT service was found to be acceptable to patients, who reported several benefits of a single SBIRT contact session delivered during an acute EC visit. These findings add to the SBIRT literature by highlighting the role of non-professional healthcare workers in delivering a low-intensity SBIRT service feasible to implement in low-resourced settings.
Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer’s disease
Authors: Cherry Jonathan D. , Esnault Camille D. , Baucom Zachary H. , Tripodis Yorghos , Huber Bertrand R. , Alvarez Victor E. , Stein Thor D. , Dickson Dennis W. , McKee Ann C.
Published: May 2021

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer’s disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.
Fertilizing behavior of extract of organomineral-activated biochar: low-dose foliar application for promoting lettuce growth
Authors: Kumar Abhay , Joseph Stephen , Graber Ellen R. , Taherymoosavi Sara , Mitchell David R. G. , Munroe Paul , Tsechansky Ludmila , Lerdahl Ove , Aker Walter , Sæbø Mona
Published: May 2021

Background

Fostering plant growth and improving agricultural yields by adding “macro”-sized biochar to soil has been extensively explored. However, the impact and mechanism of action of aqueous extracts of biochar applied as foliar fertilizer on plant growth and physiology is poorly understood, and was the objective of this study. Extracts were produced from biochars derived from pine wood:clay:sand (PCS-BC; 70:15:15) and wheat straw:bird manure (WB-BC; 50:50) and tested at two dilutions each. The plant influence of the biochar extracts and dilutions were compared with chemical fertilizer made up to the same minor trace element compositions as the applied extracts and a control treatment consisting of only deionized water.

Results

The WB-BC extract was more alkaline than the PCS-BC extract and exhibited higher electrical conductivity values. Similar to the biochars from which they were derived, the WB-BC extract had higher concentrations of dissolved mineral elements and organic matter than the PCS-BC extract. Despite major differences in chemical composition between the PCS-BC and WB-BC extracts, there was virtually no difference in plant performance between them at any chosen dilution. Foliar application of PCS25, WB50, and WB100 led to a significant increase in the plant fresh biomass in comparison to their corresponding chemical fertilizer and to deionized water. Plant growth parameters including number of leaves and chlorophyll contents in plants treated with biochar extract foliar sprays were significantly higher than in all the other treatments. Electron microscopy and spectroscopy studies showed the deposition of macro- and nanoscale organomineral particles and agglomerates on leaf surfaces of the examined PCS25-treated plant. Detailed study suggests that carbon nanomaterials and TiO2 or Si-rich nanoscale organomineral complexes or aluminosilicate compounds from biochar extract were main contributors to increased plant growth and improved plant performance.

Conclusion

These results suggest that biochar extracts have the potential to be used as nanofertilizer foliar sprays for enhancing plant growth and yield.