bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of transformational leadership, job demands and job resources for patient safety culture in Norwegian nursing homes: a cross-sectional study
Authors: Seljemo Camilla , Viksveen Petter , Ree Eline
Published: August 2020

Background

Transformational leadership style is considered to be of importance to increase patient safety, to facilitate a balance between job resources and job demands, and to create a sound patient safety culture within health care services. However, there is limited research assessing these associations within the context of nursing homes. The aim of this study was to assess the association between transformational leadership, job demands and job resources; and patient safety culture and employees’ overall perception of patient safety in nursing homes.

Method

A cross-sectional survey of employees in four Norwegian nursing homes was conducted (N = 165). Multiple hierarchical regression analysis was used to assess the explained variance of transformational leadership, job demands and job resources on patient safety culture and overall perception of patient safety.

Results

Transformational leadership explained 47.2% of the variance in patient safety culture and 25.4% of overall perception of patient safety, controlling for age and gender (p < 0.001). Additionally, job demands and job resources explained 7.8% of patient safety culture and 4.7% of overall perception of patient safety (p < 0.001).

Conclusion

Implementing transformational leadership style may be important in creating and sustaining sound patient safety culture in nursing homes. Furthermore, leaders should make an effort to facilitate a good work environment with an optimal balance between job demands and job resources, as this in turn might have a positive influence on patient safety culture.
Motivations, experiences and aspirations of trainee nursing associates in England: a qualitative study
Authors: King Rachel , Ryan Tony , Wood Emily , Tod Angela , Robertson Steve
Published: August 2020

Background

The nursing associate role was developed in England in response to the ‘Shape of Caring’ review. It has been implemented to fulfil two aims; to bridge the gap between registered nurses and healthcare assistants, and to provide an alternative route into registered nursing in light of workforce shortages.

Other high income countries deploy second level nurses within their healthcare systems, however the UK has a turbulent history with such roles. The previous state enrolled nurse was phased out in the 1990s, and more recently the assistant practitioner (AP) role has faced wide variation in titles, scope and pay. Little is known about those who have embarked on the new nursing associate training course and their experiences of the role.

Methods

An exploratory qualitative study was undertaken using focus groups of trainee nursing associates to generate in-depth discussion about their motivations, experiences of training, and career aspirations.

Three focus groups (n = 15) took place in December 2018 using a purposive sample of trainee nursing associates registered at a University in the North of England. Two researchers facilitated each group discussion at a time and place convenient for participants. The discussions were audio recorded, transcribed and data was analysed thematically.

Results

This study found that trainee nursing associates are motivated by affordable, local, career development. During training they face challenges relating to clinical support, academic workload and uncertainty about future career opportunities. They experience role ambiguity both individually and across the wider organisation. Trainee nursing associates rely on broad support networks to build their occupational identity.

Conclusions

The barriers and facilitators of trainee nursing associate personal development have implications for policy and practice relating to recruitment and retention. The results increase our understanding of this emerging role, and have informed the development of a larger longitudinal cohort study. Further research is required to evaluate the impact of this new role.
Planning the scale up of brief psychological interventions using theory of change
Authors: Fuhr Daniela C. , Acarturk Ceren , Sijbrandij Marit , Brown Felicity L. , Jordans Mark J. D. , Woodward Aniek , McGrath Michael , Sondorp Egbert , Ventevogel Peter , Ikkursun Zeynep , El Chammay Rabih , Cuijpers Pim , Roberts Bayard
Published: August 2020

Background

A large mental health treatment gap exists among conflict-affected populations, and Syrian refugees specifically. Promising brief psychological interventions for conflict-affected populations exist such as the World Health Organization’s Problem Management Plus (PM+) and the Early Adolescent Skills for Emotions (EASE) intervention, however, there is limited practical guidance for countries of how these interventions can be taken to scale. The aim of this study was to unpack pathways for scaling up PM+ and EASE for Syrian refugees.

Methods

We conducted three separate Theory of Change (ToC) workshops in Turkey, the Netherlands, and Lebanon in which PM+ and EASE are implemented for Syrian refugees. ToC is a participatory planning process involving key stakeholders, and aims to understand a process of change by mapping out intermediate and long-term outcomes on a causal pathway. 15–24 stakeholders were invited per country, and they participated in a one-day interactive ToC workshop on scaling up.

Results

A cross-country ToC map for scale up brief psychological interventions was developed which was based on three country-specific ToC maps. Two distinct causal pathways for scale up were identified (a policy and financing pathway, and a health services pathway) which are interdependent on each other. A list of key assumptions and interventions which may hamper or facilitate the scaling up process were established.

Conclusion

ToC is a useful tool to help unpack the complexity of scaling up. Our approach highlights that scaling up brief psychological interventions for refugees builds on structural changes and reforms in policy and in health systems. Both horizontal and vertical scale up approaches are required to achieve sustainability. This paper provides the first theory-driven map of causal pathways to help support the scaling-up of evidence-based brief psychological interventions for refugees and populations in global mental health more broadly.
Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease
Authors: Winkler Thomas W. , Grassmann Felix , Brandl Caroline , Kiel Christina , Günther Felix , Strunz Tobias , Weidner Lorraine , Zimmermann Martina E. , Korb Christina A. , Poplawski Alicia , Schuster Alexander K. , Müller-Nurasyid Martina , Peters Annette , Rauscher Franziska G. , Elze Tobias , Horn Katrin , Scholz Markus , Cañadas-Garre Marisa , McKnight Amy Jayne , Quinn Nicola , Hogg Ruth E. , Küchenhoff Helmut , Heid Iris M. , Stark Klaus J. , Weber Bernhard H. F.
Published: August 2020

Background

Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD.

Methods

To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and via an automated machine learning approach for > 170,000 photographs from UKBB. We searched for early AMD loci via GWAS and via a candidate approach based on 14 previously suggested early AMD variants.

Results

Altogether, we identified 10 independent loci with statistical significance for early AMD: (i) 8 from our GWAS with genome-wide significance (P < 5 × 10− 8), (ii) one previously suggested locus with experiment-wise significance (P < 0.05/14) in our non-overlapping data and with genome-wide significance when combining the reported and our non-overlapping data (together 17,539 cases, 105,395 controls), and (iii) one further previously suggested locus with experiment-wise significance in our non-overlapping data. Of these 10 identified loci, 8 were novel and 2 known for early AMD. Most of the 10 loci overlapped with known advanced AMD loci (near ARMS2/HTRA1, CFH, C2, C3, CETP, TNFRSF10A, VEGFA, APOE), except two that have not yet been identified with statistical significance for any AMD. Among the 17 genes within these two loci, in-silico functional annotation suggested CD46 and TYR as the most likely responsible genes. Presence or absence of an early AMD effect distinguished the known pathways of advanced AMD genetics (complement/lipid pathways versus extracellular matrix metabolism).

Conclusions

Our GWAS on early AMD identified novel loci, highlighted shared and distinct genetics between early and advanced AMD and provides insights into AMD etiology. Our data provide a resource comparable in size to the existing IAMDGC data on advanced AMD genetics enabling a joint view. The biological relevance of this joint view is underscored by the ability of early AMD effects to differentiate the major pathways for advanced AMD.
Association of blood pressure with cognitive function at midlife: a Mendelian randomization study
Authors: Sun Daokun , Thomas Emy A. , Launer Lenore J. , Sidney Stephen , Yaffe Kristine , Fornage Myriam
Published: August 2020

Background

Whether high blood pressure has a causal effect on cognitive function as early as middle age is unclear. We investigated whether high blood pressure (BP) causally impairs cognitive function at midlife using Mendelian Randomization (MR).

Methods

We applied a two-sample MR approach to investigate the causal relationship between BP and midlife cognitive performance measured by the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and Stroop Interference test. We used a total of 109 genetic polymorphisms with established associations with BP as instrumental variables and estimated gene-cognitive function association in 1369 middle-aged adults (Mean age (SD): 50.8 (3.3), 54.0% women) from the CARDIA study.

Results

A 10 mmHg increment in genetically-predicted systolic, diastolic, or pulse pressure was associated with a 4.9 to 7.7-point lower DSST score (P = 0.002, SBP; P = 0.005, DBP and P = 0.008, PP), while a 10 mmHg increment in genetically-predicted SBP was associated with a 0.7 point lower RAVLT and a 2.3 point higher Stroop (P = 0.046 and 0.011, respectively).

Conclusions

This MR analysis shows that high BP, especially SBP, is causally associated with poorer processing speed, verbal memory, and executive function during midlife. These findings emphasize the need for further investigation of the role and mechanisms of BP dysregulation on cognitive health in middle age and perhaps, more broadly, across the lifespan.
CXCR4+ cells are increased in lung tissue of patients with idiopathic pulmonary fibrosis
Authors: Jaffar Jade , Griffiths Kate , Oveissi Sara , Duan Mubing , Foley Michael , Glaspole Ian , Symons Karen , Organ Louise , Westall Glen
Published: August 2020

Background

CXCR4, a transmembrane-receptor located on epithelial cells that is activated by CXCL12, may have a role in IPF via migration of CXCR4+ fibrocytes to the lung. However, its expression has not been fully characterised in idiopathic pulmonary fibrosis (IPF) or other fibrotic interstitial lung diseases (ILDs). CXCL12 is constitutively expressed in the bone marrow, and levels of CXCR4 regulate control of this signalling pathway. The aim of this study was to profile the expression of CXCR4 in lung tissue and peripheral circulation of patients with IPF and other fibrotic ILDs.

Methods

Expression of CXCR4 on peripheral blood mononuclear cells (PBMCs) was examined by flow cytometry in 20 patients with IPF and 10 age-matched non-disease control (NDC) donors. Levels of CXCL12 in human plasma were measured by ELISA. Expression of CXCR4, CXCL12, CD45, and e-cadherin was assessed in IPF (n = 10), other fibrotic ILD (n = 8) and NDC (n = 10) lung tissue by multiplex immunohistochemistry (OPAL) and slides were scanned using a Vectra 3 scanner. Cells were quantified with computer automated histological analysis software (HALO).

Results

In blood, the number of CXCR4+ cells was lower but the level of CXCL12 was higher in patients with IPF compared to NDC donors. Elevated CXCR4 expression was detected in lung tissue from patients with IPF and other fibrotic ILDs compared to NDC. There were higher levels of CXCR4+/e-cadherin+/CXCL12+ (epithelial) cells in IPF lung tissue compared to NDC, but there was no difference in the numbers of CXCR4+/CD45+/CXCL12+ (myeloid) cells between the two groups.

Conclusions

This report demonstrates that CXCR4 is overexpressed not only in IPF but also in other ILDs and expression is particularly prominent within both honeycomb cysts and distal airway epithelium. This observation supports the hypothesis that CXCR4 may drive tissue fibrosis through binding its specific ligand CXCL12. Although CXCR4 expressing cells could be either of epithelial or myeloid origin it appears that the former is more prominent in IPF lung tissue. Further characterization of the cells of the honeycomb cyst may lead to a better understanding of the fibrogenic processes in IPF and other end-stage fibrotic ILDs.
CircRNA hsa_circRNA_0001776 inhibits proliferation and promotes apoptosis in endometrial cancer via downregulating LRIG2 by sponging miR-182
Authors: Jia Youjuan , Liu Meijuan , Wang Shuxia
Published: August 2020

Background

Endometrial cancer (EC) is a common malignancy of the female reproductive system. Circular RNAs (circRNAs) were demonstrated to exert critical roles in cancers, including EC. This study aimed to investigate the effects of hsa_circRNA_0001776 (circ_0001776) on EC.

Methods

Real-time quantitative PCR (RT-qPCR) was used to measure circ_0001776, microRNA-182 (miR-182) and leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) expression. The diagnostic and prognostic values of circ_0001776 were identified by receiver operating characteristic (ROC) curve analysis and survival analysis, respectively. RNase R digestion was used to characterize circ_0001776, and the localization of circ_0001776 was evaluated by cell fractionation assay. Then, cell counting kit-8 (CCK-8), colony formation, and flow cytometry analysis were used to detect cell proliferation and apoptosis, respectively. The real-time glycolytic rate (ECAR) and lactate production were measured by extracellular flux analysis and a lactate assay kit, respectively. Bioinformatics analysis and dual-luciferase reporter assay were used to determine the interaction among circ_0001776, miR-182 and LRIG2. The protein expression of LRIG2 was determined by western blot. Moreover, circ_0001776 overexpression vector was used to upregulate circ_0001776 expression in an animal tumor model.

Results

Circ_0001776 and LRIG2 were downregulated, while miR-182 was upregulated in EC tissues and cells. Low expression of circ_0001776 was correlated with the 5-year survival rate of EC patients. Upregulated circ_0001776 markedly attenuated cell proliferation and glycolysis, and enhanced cell apoptosis. Besides, circ_0001776 sponged miR-182 to regulate LRIG2 expression. Circ_0001776 could suppress EC progression by miR-182/LRIG2 axis. Furthermore, we also found that circ_0001776 significantly inhibited tumor growth in vivo.

Conclusion

Our results confirmed that circ_0001776 inhibited EC tumorigenesis and progression via miR-182/LRIG2 axis, providing a potential therapeutic target for EC.
Cryptotanshinone chemosensitivity potentiation by TW-37 in human oral cancer cell lines by targeting STAT3–Mcl-1 signaling
Authors: Yang In-Hyoung , Hong Seung-Hyun , Jung Minjung , Ahn Chi-Hyun , Yoon Hye-Jung , Hong Seong Doo , Cho Sung-Dae , Shin Ji-Ae
Published: August 2020

Background

Despite being one of the leading cancer types in the world, the diagnosis of oral cancer and its suitable therapeutic options remain limited. This study aims to investigate the single and chemosensitizing effects of TW-37, a BH3 mimetic in oral cancer, on human oral cancer cell lines.

Methods

We assessed the single and chemosensitizing effects of TW-37 in vitro using trypan blue exclusion assay, Western blotting, DAPI staining, Annexin V–FITC/PI double staining, and quantitative real-time PCR. Mcl-1 overexpression models were established by transforming vector and transient transfection was performed to test for apoptosis

Results

TW-37 enhanced the cytotoxicity of human oral cancer cell lines by inducing caspase-dependent apoptosis, which correlates with the reduction of the myeloid cell leukemia-1 (Mcl-1) expression via transcriptional and post-translational regulation. The ectopic expression of Mcl-1 partially attenuated the apoptosis-inducing capacity of TW-37 in human oral cancer cell lines. Besides, TW-37 decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and nuclear translocation in human oral cancer cell lines at the early time points. Furthermore, TW-37 potentiated chemosusceptibility of cryptotanshinone in human oral cancer cell lines by suppressing STAT3–Mcl-1 signaling compared with either TW-37 or cryptotanshinone alone, resulting in potent apoptosis.

Conclusions

This study not only unravels the single and chemosensitizing effects of TW-37 for treatment of human oral cancer but also highlights the likelihood of TW-37 as a good therapeutic strategy to enhance the prognosis of patients with oral cancer in the future.
High CENPM mRNA expression and its prognostic significance in hepatocellular carcinoma: a study based on data mining
Authors: Wu Zeng-hong , Yang Dong-liang
Published: August 2020

Background

Hepatocellular carcinoma (HCC) is a high mortality disease, the fifth most general cancer worldwide, and the second leading to cancer-related deaths, with more than 500,000 new patients diagnosed each year. First, the high expression of centromere M (CENPM) in mammary gland tissue of b-catenin transformed mice was identified.

Materials and methods

In our study, we evaluated the expression of CENPM in hepatocellular carcinoma based on data obtained from an online database. Multivariate analysis showed that the expression of CENPM and M classification was an independent prognostic factor for patients with hepatocellular carcinoma.

Results

Survival analysis showed that patients with high CENPM had a worse prognosis than patients with low CENPM (P < 0.01). A multivariate Cox regression hazard model showed that B cells, CD8+ T cells, macrophages, and dendritic cells infiltrated by immune cells were statistically significant in liver cancer (P < 0.05). Using the network, the 50 most frequently changed neighbor genes of CENPM were shown, and the most common change was RAD21 (18.3%).

Conclusion

Our study found that the expression of CENPM was significantly increased in patients with hepatocellular carcinoma, and it was related to a variety of clinical characteristics, its correlation with the level of immune infiltration and poor prognosis, so CENPM can be used as a useful prognosis for patients’ markers and HCC.
Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017–2019
Authors: Agaba Bosco B. , Anderson Karen , Gresty Karryn , Prosser Christiane , Smith David , Nankabirwa Joaniter I. , Nsobya Sam , Yeka Adoke , Opigo Jimmy , Gonahasa Samuel , Namubiru Rhoda , Arinaitwe Emmanuel , Mbaka Paul , Kissa John , Won Sungho , Lee Bora , Lim Chae Seung , Karamagi Charles , Cunningham Jane , Nakayaga Joan K. , Kamya Moses R. , Cheng Qin
Published: August 2020

Background

Histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) are the only RDTs recommended for malaria diagnosis in Uganda. However, the emergence of Plasmodium falciparum histidine rich protein 2 and 3 (pfhrp2 and pfhrp3) gene deletions threatens their usefulness as malaria diagnostic and surveillance tools. The pfhrp2 and pfhrp3 gene deletions surveillance was conducted in P. falciparum parasite populations in Uganda.

Methods

Three-hundred (n = 300) P. falciparum isolates collected from cross-sectional malaria surveys in symptomatic individuals in 48 districts of eastern and western Uganda were analysed for the presence of pfhrp2 and pfhrp3 genes. Presence of parasite DNA was confirmed by PCR amplification of the 18s rRNA gene, msp1 and msp2 single copy genes. Presence or absence of deletions was confirmed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCR.

Results

Overall, pfhrp2 and pfhrp3 gene deletions were detected in 29/300 (9.7%, 95% CI 6.6–13.6%) parasite isolates. The pfhrp2 gene was deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) isolates, pfhrp3 in 9/300 (3.0%, 95% CI 1.4–5.6%) while both pfhrp2 and pfhrp3 were deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) parasite isolates. Proportion of pfhrp2/3 deletions was higher in the eastern 14.7% (95% CI 9.7–20.0%) compared to the western region 3.1% (95% CI 0.8–7.7%), p = 0.001. Geographical location was associated with gene deletions aOR 6.25 (2.02–23.55), p = 0.003.

Conclusions

This is the first large-scale survey reporting the presence of pfhrp2/3 gene deletions in P. falciparum isolates in Uganda. Roll out of RDTs for malaria diagnosis should take into consideration the existence of pfhrp2/3 gene deletions particularly in areas where they were detected. Periodic pfhrp2/3 surveys are recommended to inform future decisions for deployment of alternative RDTs.
Human plasma plasminogen internalization route in Plasmodium falciparum-infected erythrocytes
Authors: El Chamy Maluf Sarah , Icimoto Marcelo Yudi , Melo Pollyana Maria Saud , Budu Alexandre , Coimbra Rita , Gazarini Marcos Leoni , Carmona Adriana Karaoglanovic
Published: August 2020

Background

The intra-erythrocytic development of the malaria parasite Plasmodium falciparum depends on the uptake of a number of essential nutrients from the host cell and blood plasma. It is widely recognized that the parasite imports low molecular weight solutes from the plasma and the consumption of these nutrients by P. falciparum has been extensively analysed. However, although it was already shown that the parasite also imports functional proteins from the vertebrate host, the internalization route through the different infected erythrocyte membranes has not yet been elucidated. In order to further understand the uptake mechanism, the study examined the trafficking of human plasminogen from the extracellular medium into P. falciparum-infected red blood cells.

Methods

Plasmodium falciparum clone 3D7 was cultured in standard HEPES-buffered RPMI 1640 medium supplemented with 0.5% AlbuMAX. Exogenous human plasminogen was added to the P. falciparum culture and the uptake of this protein by the parasites was analysed by electron microscopy and Western blotting. Immunoprecipitation and mass spectrometry were performed to investigate possible protein interactions that may assist plasminogen import into infected erythrocytes. The effect of pharmacological inhibitors of different cellular physiological processes in plasminogen uptake was also tested.

Results

It was observed that plasminogen was selectively internalized by P. falciparum-infected erythrocytes, with localization in plasma membrane erythrocyte and parasite’s cytosol. The protein was not detected in parasitic food vacuole and haemoglobin-containing vesicles. Furthermore, in erythrocyte cytoplasm, plasminogen was associated with the parasite-derived membranous structures tubovesicular network (TVN) and Maurer’s clefts. Several proteins were identified in immunoprecipitation assay and may be involved in the delivery of plasminogen across the P. falciparum multiple compartments.

Conclusion

The findings here reported reveal new features regarding the acquisition of plasma proteins of the host by P. falciparum-infected erythrocytes, a mechanism that involves the exomembrane system, which is distinct from the haemoglobin uptake, clarifying a route that may be potentially targeted for inhibition studies.
Therapeutic monoclonal antibody targeting of neuronal pentraxin receptor to control metastasis in gastric cancer
Authors: Kanda Mitsuro , Shimizu Dai , Sawaki Koichi , Nakamura Shunsuke , Umeda Shinichi , Miwa Takashi , Tanaka Haruyoshi , Tanaka Chie , Hayashi Masamichi , Iguchi Yohei , Yamada Suguru , Katsuno Masahisa , Kodera Yasuhiro
Published: August 2020

Background

Controlling metastasis is essential for improving the prognosis of patients with gastric cancer (GC). Here, we aimed to identify a molecule required for GC metastasis and to investigate its potential utility as a target for the development of therapeutic antibodies (Abs).

Methods

Transcriptome and bioinformatics analyses of human GC cell lines identified the neuronal pentraxin receptor (NPTXR) as a candidate molecule. NPTXR function was probed by modulating its expression in GC cells and assessing the effects on intracellular signaling and malignant behaviors in vitro and in mouse xenograft models. We also generated anti-NPTXR Abs and Nptxr−/− mice, and assessed the clinical significance of NPTXR expression in GC specimens.

Results

NPTXR mRNA expression in clinical specimens was associated with disease progression and was significantly higher in tissues from GC patients with distant metastasis compared with those without. NPTXR regulated expression of genes involved in metastatic behaviors as well as activation of the PI3K–AKT–mTOR, FAK–JNK, and YAP signaling pathways. NPTXR silencing promoted caspase-mediated apoptosis and attenuated GC cell proliferation, cell cycle progression, migration, invasion, adhesion, stem cell-like properties, and resistance to 5-fluorouracil in vitro, and also inhibited the tumorigenicity of GC cells in vivo. Anti-NPTXR Abs inhibited GC peritoneal metastasis in mice. Nptxr−/− mice showed no abnormalities in reproduction, development, metabolism, or motor function.

Conclusions

NPTXR plays an essential role in controlling the malignant behavior of GC cells in vitro and in vivo. NPTXR-targeting Abs may thus have utility as novel diagnostic tools and/or treatment modalities for GC.
The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19
Authors: Xu Yi , Baylink David J. , Chen Chien-Shing , Reeves Mark E. , Xiao Jeffrey , Lacy Curtis , Lau Eric , Cao Huynh
Published: August 2020

The coronavirus disease 2019 (COVID-19) pandemic has led to a declaration of a Public Health Emergency of International Concern by the World Health Organization. As of May 18, 2020, there have been more than 4.7 million cases and over 316,000 deaths worldwide. COVID-19 is caused by a highly infectious novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to an acute infectious disease with mild-to-severe clinical symptoms such as flu-like symptoms, fever, headache, dry cough, muscle pain, loss of smell and taste, increased shortness of breath, bilateral viral pneumonia, conjunctivitis, acute respiratory distress syndromes, respiratory failure, cytokine release syndrome (CRS), sepsis, etc. While physicians and scientists have yet to discover a treatment, it is imperative that we urgently address 2 questions: how to prevent infection in immunologically naive individuals and how to treat severe symptoms such as CRS, acute respiratory failure, and the loss of somatosensation. Previous studies from the 1918 influenza pandemic have suggested vitamin D’s non-classical role in reducing lethal pneumonia and case fatality rates. Recent clinical trials also reported that vitamin D supplementation can reduce incidence of acute respiratory infection and the severity of respiratory tract diseases in adults and children. According to our literature search, there are no similar findings of clinical trials that have been published as of July 1st, 2020, in relation to the supplementation of vitamin D in the potential prevention and treatment for COVID-19. In this review, we summarize the potential role of vitamin D extra-renal metabolism in the prevention and treatment of the SARS-CoV-2 infection, helping to bring us slightly closer to fulfilling that goal. We will focus on 3 major topics here:

Vitamin D might aid in preventing SARS-CoV-2 infection:

Vitamin D: Overview of Renal and Extra-renal metabolism and regulation.

Vitamin D: Overview of molecular mechanism and multifaceted functions beyond skeletal homeostasis.

Vitamin D: Overview of local immunomodulation in human infectious diseases.

Anti-viral infection.

Anti-malaria and anti-systemic lupus erythematosus (SLE).

Vitamin D might act as a strong immunosuppressant inhibiting cytokine release syndrome in COVID-19:

Vitamin D: Suppression of key pro-inflammatory pathways including nuclear factor kappa B (NF-kB), interleukin-6 (IL-6), and tumor necrosis factor (TNF).

Vitamin D might prevent loss of neural sensation in COVID-19 by stimulating expression of neurotrophins like Nerve Growth Factor (NGF):

Vitamin D: Induction of key neurotrophic factors.

.
Rectus femoris hyperreflexia contributes to Stiff-Knee gait after stroke
Authors: Akbas Tunc , Kim Kyoungsoon , Doyle Kathleen , Manella Kathleen , Lee Robert , Spicer Patrick , Knikou Maria , Sulzer James
Published: August 2020

Background

Stiff-Knee gait (SKG) after stroke is often accompanied by decreased knee flexion angle during the swing phase. The decreased knee flexion has been hypothesized to originate from excessive quadriceps activation. However, it is unclear whether hyperreflexia plays a role in this activation. The goal of this study was to establish the relationship between quadriceps hyperreflexia and knee flexion angle during walking in post-stroke SKG.

Methods

The rectus femoris (RF) H-reflex was recorded in 10 participants with post-stroke SKG and 10 healthy controls during standing and walking at the pre-swing phase. In order to attribute the pathological neuromodulation to quadriceps muscle hyperreflexia and activation, healthy individuals voluntarily increased quadriceps activity using electromyographic (EMG) feedback during standing and pre-swing upon RF H-reflex elicitation.

Results

We observed a negative correlation (R = − 0.92, p = 0.001) between knee flexion angle and RF H-reflex amplitude in post-stroke SKG. In contrast, H-reflex amplitude in healthy individuals in presence (R = 0.47, p = 0.23) or absence (R = − 0.17, p = 0.46) of increased RF muscle activity was not correlated with knee flexion angle. We observed a body position-dependent RF H-reflex modulation between standing and walking in healthy individuals with voluntarily increased RF activity (d = 2.86, p = 0.007), but such modulation was absent post-stroke (d = 0.73, p = 0.296).

Conclusions

RF reflex modulation is impaired in post-stroke SKG. The strong correlation between RF hyperreflexia and knee flexion angle indicates a possible regulatory role of spinal reflex excitability in post-stroke SKG. Interventions targeting quadriceps hyperreflexia could help elucidate the causal role of hyperreflexia on knee joint function in post-stroke SKG.
3D characterization of walnut morphological traits using X-ray computed tomography
Authors: Bernard Anthony , Hamdy Sherif , Le Corre Laurence , Dirlewanger Elisabeth , Lheureux Fabrice
Published: August 2020

Background

Walnuts are grown worldwide in temperate areas and producers are facing an increasing demand. In a climate change context, the industry also needs cultivars that provide fruits of quality. This quality includes satisfactory filling ratio, thicker shell, ease of cracking, smooth shell and round-shaped walnut, and larger nut size. These desirable traits have been analysed so far using calipers or micrometers, but it takes a lot of time and requires the destruction of the sample. A challenge to take up is to develop an accurate, fast and non-destructive method for quality-related and morphometric trait measurements of walnuts, that are used to characterize new cultivars or collections in any germplasm management process.

Results

In this study, we develop a method to measure different morphological traits on several walnuts simultaneously such as morphometric traits (nut length, nut face and profile diameters), traits that previously required opening the nut (shell thickness, kernel volume and filling kernel/nut ratio) and traits that previously were difficult to quantify (shell rugosity, nut sphericity, nut surface area and nut shape). These measurements were obtained from reconstructed 3D images acquired by X-ray computed tomography (CT). A workflow was created including several steps: noise elimination, walnut individualization, properties extraction and quantification of the different parts of the fruit. This method was applied to characterize 50 walnuts of a part of the INRAE walnut germplasm collection made of 161 unique accessions, obtained from the 2018 harvest. Our results indicate that 50 walnuts are sufficient to phenotype the fruit quality of one accession using X-ray CT and to find correlations between the morphometric traits. Our imaging workflow is suitable for any walnut size or shape and provides new and more accurate measurements.

Conclusions

The fast and accurate measurement of quantitative traits is of utmost importance to conduct quantitative genetic analyses or cultivar characterization. Our imaging workflow is well adapted for accurate phenotypic characterization of a various range of traits and could be easily applied to other important nut crops.
Does arthroscopic repair show superiority over open repair of lateral ankle ligament for chronic lateral ankle instability: a systematic review and meta-analysis
Authors: Zhi Xiaosong , Lv Zhuman , Zhang Chen , Kong Changwang , Wei Shijun , Xu Feng
Published: August 2020

Background

There is still no definite consensus on whether arthroscopic repair shows superiority over open repair for chronic lateral ankle instability. We conducted a systematic review and meta-analysis of the current comparative studies to make a generalized analysis.

Methods

PubMed, Embase, and Web of Science databases were searched from inception to April 2020. Included studies were assessed by the level of evidence and quality of evidence (Cochrane Handbook or MINORS). The process of data extraction was conducted by two independent authors. The comparative results of clinical outcomes, stress radiographic outcomes, and complication rates between two groups were pooled. Statistical analysis was performed using STATA.

Results

Nine comparative studies for a total of 473 patients (250 arthroscopic repair, 223 open repair) were included. For the clinical outcomes, a significant difference was found in favor of arthroscopic repair with regard to AOFAS scores (MD 0.32, 95% CI 0.12 to 0.53,I2= 7.7%,P= .370) and VAS scores (MD − 0.30, 95% CI − 0.54 to − 0.05,I2= 48.3%,P= .102). No significant difference was found regarding to stress radiographic outcomes. Importantly, the total complication rate (RR 0.88, 95% CI 0.51 to 1.49,I2= 0%,P= .957) as well as nerve complication rate (RR 1.21, 95% CI 0.53 to 2.75,I2= 0%,P= .975) of arthroscopic repair group is not significantly different to that of open repair group.

Conclusions

Arthroscopic repair for lateral ankle instability shows excellent clinical results comparable to open repair. Especially, arthroscopic repair might alleviate more pain due to the minimally invasive procedure. Patients receiving arthroscopic repair do not result in a higher total complication rate and nerve injury rate.
What we already know about rhubarb: a comprehensive review
Authors: Xiang Hong , Zuo Jiaxin , Guo Fangyue , Dong Deshi
Published: August 2020

Rhubarb (also named Rhei or Dahuang), one of the most ancient and important herbs in traditional Chinese medicine (TCM), belongs to theRheum L.genus from the Polygonaceae family, and its application can be traced back to 270 BC in “Shen Nong Ben Cao Jing”. Rhubarb has long been used as an antibacterial, anti-inflammatory, anti-fibrotic and anticancer medicine in China. However, for a variety of reasons, such as origin, variety and processing methods, there are differences in the effective components of rhubarb, which eventually lead to decreased quality and poor efficacy. Additionally, although some papers have reviewed the relationship between the active ingredients of rhubarb and pharmacologic actions, most studies have concentrated on one or several aspects, although there has been great progress in rhubarb research in recent years. Therefore, this review aims to summarize recent studies on the geographic distribution, taxonomic identification, pharmacology, clinical applications and safety issues related to rhubarb and provide insights into the further development and application of rhubarb in the future.
PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection
Authors: Tang Zheng-Zheng , Sliwoski Gregory R. , Chen Guanhua , Jin Bowen , Bush William S. , Li Bingshan , Capra John A.
Published: August 2020

Germline disease-causing variants are generally more spatially clustered in protein 3-dimensional structures than benign variants. Motivated by this tendency, we develop a fast and powerful protein-structure-based scan (PSCAN) approach for evaluating gene-level associations with complex disease and detecting signal variants. We validate PSCAN’s performance on synthetic data and two real data sets for lipid traits and Alzheimer’s disease. Our results demonstrate that PSCAN performs competitively with existing gene-level tests while increasing power and identifying more specific signal variant sets. Furthermore, PSCAN enables generation of hypotheses about the molecular basis for the associations in the context of protein structures and functional domains.
Differential contribution of Anopheles coustani and Anopheles arabiensis to the transmission of Plasmodium falciparum and Plasmodium vivax in two neighbouring villages of Madagascar
Authors: Goupeyou-Youmsi Jessy , Rakotondranaivo Tsiriniaina , Puchot Nicolas , Peterson Ingrid , Girod Romain , Vigan-Womas Inès , Paul Richard , Ndiath Mamadou Ousmane , Bourgouin Catherine
Published: August 2020

Background

Malaria is still a heavy public health concern in Madagascar. Few studies combining parasitology and entomology have been conducted despite the need for accurate information to design effective vector control measures. In a Malagasy region of moderate to intense transmission of bothPlasmodium falciparumandP. vivax, parasitology and entomology have been combined to survey malaria transmission in two nearby villages.

Methods

Community-based surveys were conducted in the villages of Ambohitromby and Miarinarivo at three time points (T1, T2 and T3) during a single malaria transmission season. Human malaria prevalence was determined by rapid diagnostic tests (RDTs), microscopy and real-time PCR. Mosquitoes were collected by human landing catches and pyrethrum spray catches and the presence ofPlasmodiumsporozoites was assessed by TaqMan assay.

Results

Malaria prevalence was not significantly different between villages, with an average of 8.0% by RDT, 4.8% by microscopy and 11.9% by PCR. This was mainly due toP. falciparumand to a lesser extent toP. vivax. However, there was a significantly higher prevalence rate as determined by PCR at T2 ($$\chi_{2}^{2}$$χ22= 7.46,P= 0.025). Likewise, mosquitoes were significantly more abundant at T2 ($$\chi_{2}^{2}$$χ22= 64.8,P< 0.001), especially in Ambohitromby. At T1 and T3 mosquito abundance was higher in Miarinarivo than in Ambohitromby ($$\chi_{2}^{2}$$χ22= 14.92,P< 0.001). Of 1550Anophelesmosquitoes tested, 28 (1.8%) were found carryingPlasmodiumsporozoites. The entomological inoculation rate revealed thatAnopheles coustaniplayed a major contribution in malaria transmission in Miarinarivo, being responsible of 61.2 infective bites per human (ib/h) during the whole six months of the survey, whereas, it wasAn. arabiensis, with 36 ib/h, that played that role in Ambohitromby.

Conclusions

Despite a similar malaria prevalence in two nearby villages, the entomological survey showed a different contribution ofAn. coustaniandAn. arabiensisto malaria transmission in each village. Importantly, the suspected secondary malaria vectorAn. coustani, was found playing the major role in malaria transmission in one village. This highlights the importance of combining parasitology and entomology surveys for better targeting local malaria vectors. Such study should contribute to the malaria pre-elimination goal established under the 2018–2022 National Malaria Strategic Plan.
Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis
Authors: Siafis Spyridon , Çıray Oğulcan , Schneider-Thoma Johannes , Bighelli Irene , Krause Marc , Rodolico Alessandro , Ceraso Anna , Deste Giacomo , Huhn Maximilian , Fraguas David , Mavridis Dimitris , Charman Tony , Murphy Declan G. , Parellada Mara , Arango Celso , Leucht Stefan
Published: August 2020

Background

Placebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms.

Methods

We searched ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019) for randomized pharmacological and dietary supplement placebo-controlled trials (RCTs) with a minimum of seven days of treatment. Single-group meta-analyses were conducted using a random-effects model. Standardized mean changes (SMC) of core symptoms in placebo arms were the primary outcomes and placebo positive response rates were a secondary outcome. Predictors of placebo response were investigated with meta-regression analyses. The protocol was registered with PROSPERO ID CRD42019125317.

Results

Eighty-six RCTs with 2360 participants on placebo were included in our analysis (87% in children/adolescents). The majority of trials were small, single-center with a duration of 8–12 weeks and published after 2009. Placebo response in social-communication difficulties was SMC = − 0.32, 95% CI [− 0.39, − 0.25], in repetitive behaviors − 0.23[− 0.32, − 0.15] and in scales measuring overall core symptoms − 0.36 [− 0.46, − 0.26]. Overall, 19%, 95% CI [16–22%] of participants were at least much improved with placebo. Caregiver (vs. clinician) ratings, lower risk of bias, flexible-dosing, larger sample sizes and number of sites, less recent publication year, baseline levels of irritability, and the use of a threshold of core symptoms at inclusion were associated with larger placebo response in at least a core symptom domain.

Limitations

About 40% of the trials had an apparent focus on core symptoms. Investigation of the differential impact of predictors on placebo and drug response was impeded by the use of diverse experimental interventions with essentially different mechanisms of action. An individual-participant-data meta-analysis could allow for a more fine-grained analysis and provide more informative answers.

Conclusions

Placebo response in ASD was substantial and predicted by design- and participant-related factors, which could inform the design of future trials in order to improve the detection of efficacy in core symptoms. Potential solutions could be the minimization and careful selection of study sites as well as rigorous participant enrollment and the use of measurements of change not solely dependent on caregivers.
The needle and the damage done: musculoskeletal and vascular complications associated with injected drug use
Authors: Delaney Francis T. , Stanley Emma , Bolster Ferdia
Published: August 2020

Injected drug use is associated with a wide range of medical complications which are predominantly musculoskeletal and vascular in nature. Illicit drug use is increasing worldwide. Patients with complications of injected drug use often present in a non-specific manner without a reliable clinical history. Musculoskeletal complications are typically infective in aetiology and may vary widely in severity from mild to life-threatening. A multimodal imaging approach is often required for both diagnostic imaging and image-guided sampling. Plain radiographs are often an important initial test, for example in identifying retained needles from injection. Ultrasound and CT play important roles in the assessment of complex soft tissue complications and MRI is the imaging modality of choice for bone and joint disorders. Vascular complications may be venous or arterial in nature and usually occur locally at the injection site. These complications may be related to direct injury to the vessel wall by a needle, or secondary to local infection and inflammation. A multimodal imaging strategy is also often required in the assessment of these vascular complications, typically involving a combination of ultrasound and CT. Familiarity with the multimodal imaging features of the complications related to injected drug use is crucially important as they may be rapidly progressive and life-threatening and require timely diagnosis.
Mesenchymal stromal cells protect against vascular damage and depression-like behavior in mice surviving cerebral malaria
Authors: Lima Maiara N. , Oliveira Helena A. , Fagundes Paula M. , Estato Vanessa , Silva Adriano Y. O. , Freitas Rodrigo J. R. X. , Passos Beatriz A. B. R. , Oliveira Karina S. , Batista Camila N. , Vallochi Adriana L. , Rocco Patricia R. M. , Castro-Faria-Neto Hugo C. , Maron-Gutierrez Tatiana
Published: August 2020

Background

Malaria is one of the most critical global infectious diseases. Severe systemic inflammatory diseases, such as cerebral malaria, lead to the development of cognitive and behavioral alterations, such as learning disabilities and loss of memory capacity, as well as increased anxiety and depression. The consequences are profound and usually contribute to reduce the patient’s quality of life. There are no therapies to treat the neurological sequelae of cerebral malaria. Mesenchymal stromal cells (MSCs) may be an alternative, since they have been used as therapy for neurodegenerative diseases and traumatic lesions of the central nervous system. So far, no study has investigated the effects of MSC therapy on the blood-brain barrier, leukocyte rolling and adherence in the brain, and depression like-behavior in experimental cerebral malaria.

Methods

Male C57BL/6 mice were infected with Plasmodium berghei ANKA (PbA, 1 × 106 PbA-parasitized red blood cells, intraperitoneally). At day 6, PbA-infected animals received chloroquine (25 mg/kg orally for seven consecutive days) as the antimalarial treatment and were then randomized to receive MSCs (1 × 105 cells in 0.05 ml of saline/mouse) or saline (0.05 ml) intravenously. Parasitemia, clinical score, and survival rate were analyzed throughout the experiments. Evans blue assay was performed at 6, 7, and 15 days post-infection (dpi). Behavioral tests were performed at 5 and 15 dpi. Intravital microscopy experiments and brain-derived neurotrophic factor (BDNF) protein expression analyses were performed at 7 dpi, whereas inflammatory mediators were measured at 15 dpi. In vitro, endothelial cells were used to evaluate the effects of conditioned media derived from MSCs (CMMSC) on cell viability by lactate dehydrogenase (LDH) release.

Results

PbA-infected mice presented increased parasitemia, adherent leukocytes, blood-brain barrier permeability, and reduced BDNF protein levels, as well as depression-like behavior. MSCs mitigated behavioral alterations, restored BDNF and transforming growth factor (TGF)-β protein levels, and reduced blood-brain barrier dysfunction and leukocyte adhesion in the brain microvasculature. In a cultured endothelial cell line stimulated with heme, CMMSC reduced LDH release, suggesting a paracrine mechanism of action.

Conclusion

A single dose of MSCs as adjuvant therapy protected against vascular damage and improved depression-like behavior in mice that survived experimental cerebral malaria.