bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of digital health insurance management systems in scaling health insurance coverage in low- and Middle-Income Countries: A case study from Nigeria
Authors: Okuzu Okey , Malaga Ross , Okereafor Kenneth , Amos Ujulu , Dosunmu Afolabi , Oyeneyin Abiodun , Adeoye Victor , Sambo Mohammed Nasir , Ebenso Bassey
Published: September 2022

Background

Increasing global commitment to Universal Health Coverage (UHC) in the past decade has triggered UHC-inspired reforms and investments to expand health service coverage in many Low- and Middle-Income Countries (LMICs). UHC aims to ensure that all people can access quality health services, safeguard them from public health risks and impoverishment from out-of-pocket payments for healthcare when household members are sick

Aim

This paper reviews the role of health insurance as a policy tool to address health financing as a contributory mechanism for accelerating the achievement of UHC in LMICs. We focus on Nigeria's legal framework for health insurance coverage for its whole population and the role of technology in facilitating enrollment to health insurance schemes.

Methods

From May to July 2022, we adopted a cross-sectional case study design combining: (i) a literature review of the effects of UHC with (ii) document analysis of health insurance systems in Nigeria, and (iii) secondary analysis of health insurance datasets to understand experiences of deploying MedStrat, a locally-developed digital health insurance management system, and its features that support the administration of health insurance schemes in multiple states of Nigeria. We drew on contemporary technology adoption models to triangulate diverse data analyzed from literature and documents reviews and from health insurance datasets to identify: (i) enablers of adoption of digital insurance schemes, (ii) the contribution of digital technology to expanding access to health insurance, and (iii) further scalability of digital insurance intervention.

Results

Preliminary findings suggests that digital insurance management systems can help to increase the number of enrollees for insurance especially among poor households. Three contextual enablers of adoption of digital insurance schemes were a favourable policy environment, public-private-partnerships, and sustained stakeholder engagement and training.

Discussion and conclusion

Key elements for successful scaling of digital health insurance schemes across Nigeria and similar contexts include: (i) ease of use, (ii) existing digital infrastructure to support electronic insurance systems, and (iii) trust manifested via data encryption, maintaining audit trails for all data, and in-built fraud prevention processes. Our findings affirm that digital health technology can play a role in the attainment of UHC in LMICs.
Comparison of CO2, N2, CO, H2S, CH4, and H2O adsorptions onto sI methane hydrate surface
Authors: Zhang Ming , Zhao Baoli , Li Jiahua , Li Tiantai , Li Jian
Published: September 2022

By employing molecular dynamic (MD) and density functional theory (DFT) calculations, the adsorptions of CO2, N2, CO, H2S, CH4, and H2O onto methane hydrate (MH) surface are compared in this work. The methane hydrate planes of (001) and (110) and various cleaving sites are compared with cleavage energies. MH(001) has more tendency to form when compared with MH(110) in thermodynamics. Two different terminations of MH(001) surfaces are compared, and MH(001)-I (terminated with CH4+H2O) leads to more negative adsorption energies when compared with MH(001)-II (terminated with H2O only). The priority sequence of the adsorptions can be queued as: H2O > H2S > CO2 > N2 > CH4 > CO. Namely, CO2, N2, and H2S have potential to replace CH4 in methane hydrate. The interfacial hydrogen bond and electronic interactions are clarified for the adsorptions of CO2, N2, and H2S. The hydrogen bonds tend to form between O-H atom pairs of CO2-H2O, N-H atom pairs of N2-H2O, and S-H and H-O atom pairs of H2S-H2O, respectively. The bonds are mainly contributed from the dispersion interaction between the O-2p in CO2 and H-1s in H2O, N-2p in N2 and H-1s in H2O, S-3p in H2S and H-1s in H2O, and H-1s in H2S and O-2p in H2O, respectively.
Multi-tiered systems of support for school attendance and its problems: An unlearning perspective for areas of high chronic absenteeism
Authors: Kearney Christopher A. , Graczyk Patricia A.
Published: September 2022

School attendance problems (SAPs) are a vexing challenge for many educational districts given their complexity, heterogeneity, and opacity. One potential coordinated, integrated approach to ameliorate SAPs and boost school attendance is to leverage existing school-based systems already designed to address multiple individual domains of functioning in students. Multi-tiered systems of support frameworks for school attendance and its problems have been developed but remain in the nascent stage. The purpose of this perspective article is to begin a discussion as to how such frameworks for SAPs could be fundamentally reconfigured in areas with very high rates of chronic absenteeism. Recommendations are provided at each tier, with the understanding that original notions of how tiers are ostensibly constructed and aimed must be unlearned in these circumstances.
Benchmarking the research performance of United Arab Emirates with gulf cooperation council countries – A bibliometric study
Authors: Ajayan Shalini , Balasubramanian Sreejith , Ramachandran Sunder
Published: September 2022

The research performance of a country is an indicator of its scientific progress and benchmarking it with regional countries is critical to assess a country’s regional competitiveness. This study aims to assess and benchmark the research productivity of the United Arab Emirates (UAE) against other member nations of the Gulf Cooperation Council (GCC), namely with Saudi Arabia, Oman, Kuwait, Qatar, and Bahrain, who have similar macroeconomic and socio-cultural characteristics. Scopus was used as the data source to extract the research output of each of the six countries studied for the period 1995–2019. Bibliometric indicators covering both quantity and impact of research such as publication output, citation, and collaboration indicators were used to assess the research performance of UAE and other GCC countries. The findings indicate good progress in the UAE’s overall research performance during the period of study. Also, UAE’s research performance in most of the bibliometric indicators is comparable or superior to the other GCC countries. This study is the first of its kind and addresses the dearth of bibliometric studies assessing UAE’s research productivity and GCC countries in general. The findings are useful for administrators and policymakers to benchmark the performance of the UAE with other GCC countries, including its impact, growth, and trajectories. For researchers, the study indicators and methods can be replicated to assess the overall research performance of other countries.
Subsynchronous oscillation detection via cycle-based feature extraction and weighted kernel extreme learning machine
Authors: Wang Lei , Li Tiecheng , Fan Hui , Hu Xuekai , Yang Lin , Yang Xiaomei
Published: September 2022

The fast and reliable detection of subsynchronous oscillations (SSOs) in wind farms is important for maintaining the stable operation of a power system. This paper presents a novel, SSO detection method for noisy synchrophasor data that considers the issue of detection as a binary classification (SSO and non-SSO) from the perspective of pattern recognition. The proposed algorithm easily implements cycle-based feature extraction from raw data by applying the strong period of the SSO signal, which is distinguished from noisy data. To mitigate the performance reduction of regular classifiers due to the imbalance issue caused by SSO data being substantially less than non-SSO data, a weighted kernel extreme learning machine is constructed as a classifier to implement SSO detection. Experimental studies are carried out on simulation and field data; the results show the effectiveness of the proposed algorithm for SSO detection in the case of a low SNR and of imbalance issues.
Testing non-linear effect of urbanization on environmental degradation: Cross-country evidence
Authors: Talib Mirza Nouman Ali , Hashmi Shujahat Haider , Aamir Muhammad , Khan Muhammad Asif
Published: September 2022

The contribution of structural transformation and urban development is considered crucial for the long run socio-economic growth but has adversely affected environmental sustainability over last few decades. This empirical research makes an innovative and holistic addition to the prior literature by examining the non-linear effect of economic growth and urban dynamics on environmental degradation in a comprehensive panel data of 66 countries and across respective income groups for the period 1990–2016. For empirical analysis, the robust econometric methods of two-way fixed effects (2W-FE), panel fully modified ordinary least squares (PFMOLS), and Driscoll-Kraay regressions have been applied to account for all econometric issues. The study unveils the bell-shaped effect of economic growth on environmental degradation which confirms the Environmental Kuznets Curve (EKC) and structural change hypotheses. The results of this study signifies the inverted U influence of urbanization and urban agglomerations on CO2 emissions and hence supports Ecological Modernization Theory (EMT). Our empirical findings also unfold the heterogeneous non-linear effects of urban dynamics across various income categories of selected economies. By employing the heterogeneous Dumitrescu and Hurlin (D-H) (Granger non-causality tests), the findings of this study confirm the prior estimations and establish significant unilateral and bilateral causal nexus of structural change and urban dynamics with environmental degradation. By verifying the existence of Environmental Kuznets Curve phenomenon in Low and Lower Middle Income (LLMI) and Upper Middle Income (UMI) group countries, this study necessitates for the policy makers to adopt the eco-friendly industrial and energy policies for the long run social, economic and environmental sustainability.
Distribution patterns of microplastics in subtidal sediments from the Sado river estuary and the Arrábida marine park, Portugal
Authors: Rodrigues Diana , Antunes Joana , Pais Joana , Pequeno João , Caetano Paulo Sá , Rocha Fernando , Sobral Paula , Costa Maria Helena
Published: September 2022

Understanding local accumulation patterns of microplastics in subtidal sediments is crucial to assess how available such particles are for ingestion by benthic feeders and to identify the potential pollution sources in the region upon which is urgent to act. The coastal urban centers of Setúbal and Sesimbra (Portugal) and the multiple activities taking place at the contiguous Sado estuary and in the sheltered waters of Professor Luiz Saldanha Marine Park make this a relevant case study about MPs pollution in the seabed. Here, a short-term investigation assessed the spatiotemporal distribution, abundance, and composition of MPs on the nearshore seabed. Sediment samples were monthly collected from summer 2018 to winter 2019, in six stations. Despite the differences observed in rainfall between campaigns, no distinct patterns were detected in the accumulation of MPs throughout the sampled months. Yet, strong variations occurred among stations. The abundance of MPs in the Sado estuary (1042.8 ± 430.8 items kg−1) was higher in comparison to all the stations located along the marine park (52.9 ± 31.9 items kg−1). Fragments comprised 70% of particles found in estuarine sediments, while fibers were the predominant type in marine sediments. The majority of MPs collected in the estuary shared the same size class as the best represented grain size fraction: 0.250–0.500 mm. On average, the ratio between the abundance of MPs and the abundance of meiofauna organisms was higher in the estuary, suggesting more encounter rates, by both meiofauna and their predators, with MPs. The distribution of MPs throughout the study area was moderately correlated with sediment sorting and organic matter content. Also, the distinct mineralogical content of each station indicates a reduced sediment transit between stations and consequently a weak exportation of MPs from the estuary. The majority of the polymers identified by Fourier Transform Infrared Spectroscopy was denser than seawater. Polyethylene terephthalate represented 41% of the items analyzed and was mostly assigned to fibers and fiber bundles. Unveiling the distribution patterns of MPs along this segment of the Portuguese west coast enabled to identify a high-risk area where the implementation of preventive measures is urgent.
Influence of family planning and immunization services integration on contraceptive use and family planning information and knowledge among clients: A cross-sectional analysis in urban Nigeria
Authors: Sheahan Kate L. , Speizer Ilene , Curtis Siân , Weinberger Morris , Paul John , Bennett Antonia V.
Published: September 2022

Reproductive autonomy necessitates that women have access to high quality family planning information and services. Additionally, closely spaced pregnancies increase maternal and infant morbidity and mortality. Although integrating family planning into child immunization services may increase access to information and services and postpartum contraceptive use, evidence on how integration affects service delivery and health outcomes is scarce. One limitation of previous studies is the use of binary integration measures. To address this limitation, this study applied Provider and Facility Integration Index scores to estimate associations between integration and contraceptive use, receipt of family planning information, and knowledge of family planning services availability. This study leveraged pooled cross-sectional health facility client exit interview data collected from 2,535 women in Nigeria. Provider and Facility Integration Index scores were calculated (0–10, 0 = low, 10 = high) for each facility (N = 94). The Provider Integration Index score measures provider skills and practices that support integrated service delivery; the Facility Integration Index score measures facility norms that support integrated service delivery. Logistic regression models identified associations between Provider and Facility Integration Index scores and (a) contraceptive use among postpartum women, (b) receipt of family planning information during immunization visits, and (c) correct identification of family planning service availability. Overall, 46% of women were using any method of contraception, 51% received family planning information during the immunization appointment, and 83% correctly identified family planning service availability at the facility. Mean Provider and Facility Integration Index scores were 6.46 (SD = 0.21) and 7.27 (SD = 0.18), respectively. Provider and Facility Integration Index scores were not significantly associated with postpartum contraceptive use. Facility Integration Index scores were negatively associated with receipt of family planning information. Provider Integration Index scores were positively associated with correct identification of family planning service availability. Our results challenge the position that integration provides a clear path to improved outcomes. The presence of facility and provider attributes that support integration may not result in the delivery of integrated care.
Characterization of the immune system of Ellegaard Göttingen Minipigs - An important large animal model in experimental medicine
Authors: Pernold Clara P.S. , Lagumdzic Emil , Stadler Maria , Mair Kerstin H. , Jäckel Sven , Schmitt Michael W. , Ladinig Andrea , Knecht Christian , Dürlinger Sophie , Kreutzmann Heinrich , Martin Vera , Sawyer Spencer , Saalmüller Armin
Published: September 2022

Interest in Ellegaard Göttingen Minipigs (EGMs) as a model in experimental medicine is continuously growing. The aim of this project is to increase the knowledge of the immune system of EGMs as information is still scarce. Therefore, we studied the postnatal maturation of their immune system from birth until 126 weeks of age. For the first 26 weeks of the study, animals were kept under pathogen-reduced conditions (SPF) and afterwards under conventional housing conditions. The development of the immune system was analyzed by monitoring changes in total numbers of leukocytes and lymphocytes of ten individuals and the composition of leukocyte populations by multi-color flow cytometry (FCM). We followed the presence of monocytes using monoclonal antibodies (mAbs) against CD172a+and CD163+and B cells based on the expression of CD79a. NK cells were distinguished as CD3-CD16+CD8α+/dimcells and further subdivided using NKp46 (CD335) expression into NKp46-, NKp46+, and NKp46highNK cells. T-cell receptor (TCR) γδ T cells were defined by the expression of TCR-γδ and different subsets were determined by their CD2 and perforin expression. TCR-αβ T cells were classified by their CD8β+or CD4 expression. For monitoring their differentiation, expression of CD27 and perforin was investigated for CD8β++T cells and CD8α together with CD27 for CD4+T cells. We clearly detected a postnatal development of immune cell composition and identified phenotypes indicative of differentiation within the respective leukocyte subsets. Examination of the development of the antigen-specific immune system after transfer to different distinct housing conditions and after vaccination against common porcine pathogens such as porcine circovirus 2 (PCV2) revealed a markedly increased presence of more differentiated CD8+and CD4+T cells with central and effector memory T-cell phenotypes. To complement the findings, a PCV2 vaccine-specific antigen was used forin vitrorestimulation experiments. We demonstrated antigen-specific proliferation of CD4+CD8α+CD27+central and CD4+CD8α+CD27-effector memory T cells as well as antigen-specific production of TNF-α and IFN-γ. This study of postnatal immune development defines basic cellular immune parameters of EGMs and represents an important milestone for the use of EGMs for immunological questions in experimental medicine.
Improving the immunomodulatory function of mesenchymal stem cells by defined chemical approach
Authors: Cheng Jintao , Feng Yuan , Feng Xiao , Wu Donghao , Lu Xu , Rao Zhihua , Li Cuiping , Lin Nan , Jia Changchang , Zhang Qi
Published: September 2022

Mesenchymal stem cell (MSC) is a potential therapeutic material that has self-renewal, multilineage differentiation, and immunomodulation properties. However, the biological function of MSCs may decline due to the influence of donor differences and the in vitro expansion environment, which hinders the advancement of MSC-based clinical therapy. Here, we investigated a method for improving the immunomodulatory function of MSCs with the help of small-molecule compounds, A-83-01, CHIR99021, and Y27632 (ACY). The results showed that small-molecule induced MSCs (SM-MSCs) could enhance their immunosuppressive effects on T cells and macrophages. In vivo studies showed that, in contrast to control MSCs (Ctrl-MSCs), SM-MSCs could inhibit the inflammatory response in mouse models of delayed hypersensitivity and acute peritonitis more effectively. In addition, SM-MSCs showed the stronger ability to inhibit the infiltration of pro-inflammatory T cells and macrophages. Thus, small-molecule compounds ACY could better promote the immunomodulatory effect of MSCs, indicating it could be a potential improving method in MSC culture.
Csf2ra deletion attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice
Authors: Zong Fuliang , Li Sha , Wang Yifeng , Xiao Nan , Deng Mengyun , Zhang Zhipeng , Su Duo , Gao Bo , Zhou Dongsheng , Hu Lingfei , Yang Huiying
Published: September 2022

Specific therapeutics are not available for acute lung injury (ALI) induced by ricin toxin (RT). Inhibiting the host immune response in the course of pulmonary ricinosis is hypothesized to be of benefit and can be achieved by impairing granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, thereby reducing the pro-inflammatory response to exogenous foreign body invasion. However, it is unknown whether mice with impaired GM-CSF signaling can survive after RT inhalation. To test this, colony stimulating factor 2 receptor alpha (Csf2ra) knockout (KO) mice that lack GM-CSF signaling and wild-type (WT) mice models of intratracheal exposure to a lethal dose (2× LD50) of RT were established. Survival was greater in Csf2ra KO mice 21 days after RT inhalation compared with WT mice. Highly co-expressed genes that probably attenuated the pro-inflammatory response in the lung of Csf2ra KO mice were identified. Bioinformatics analysis revealed that transcriptome changes involved mostly inflammation-related genes after RT exposure in both Csf2ra KO mice and WT mice. However, the activity levels of pro-inflammatory pathways, such as the TNF signaling pathway and NF-κB signaling pathway, in Csf2ra KO mice were significantly decreased and the degree of neutrophil chemotaxis and recruitment inhibited after RT-exposure relative to WT mice. RT-qPCR and flow cytometry validated results of RNA-Seq analysis. This work provides potential avenues for host-directed therapeutic applications that can mitigate the severity of ALI-induced by RT.
A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-κB and T cell anergy (BENTA) and literature review
Authors: Zhao Peiwei , Hu Yanqiu , Sun Dongming , Meng Qingjie , Zhang Lei , Zhang Xiankai , Tan Li , Zhang Yong , Ding Yan , He Xuelian
Published: September 2022

Germline gain-of-function (GOF) mutations in the CARD11 gene lead to a rare primary immunodeficiency disease known as B cell expansion with NF-κB and T cell anergy (BENTA). Affected patients present with a polyclonal expansion of B cells, lymphadenopathy, and splenomegaly. Herein, we report a novel germline in-frame three base-pair deletion (c.1030_1032del, p.K344del) in the CARD11 gene in a patient with atypical BENTA, presenting with a recurrent fever and B cell lymphocytosis. This mutation was inherited from his mother, who is clinically asymptomatic and had a recurrent respiratory tract infection in her childhood. In vitro functional analysis demonstrated that this variant decreased the expression level of the CARD11 protein and activated the NF-κB signal pathway, leading to a higher expression of several NF-κB target gene transcripts in HCT116 cells transfected with mutant CARD11 (K344del-CARD11) as revealed by RNA sequencing analysis. To our knowledge, only 23 BENTA patients have been identified and carried seven distinct GOF mutations in CARD11. The clinical manifestations of patients are highly heterogeneous and there was no significant correlation between genotype and phenotype. In summary, we identified a novel in-frame three base-pair deletion that may be responsible for the pathogenesis of atypical BENTA in a Chinese family. Our study expands the mutational spectrum of the CARD11 gene and may be helpful in the understanding of diseases caused by CARD11 mutations and the clinical management of BENTA.
Induction of T cell exhaustion by JAK1/3 inhibition in the treatment of alopecia areata
Authors: Dai Zhenpeng , Sezin Tanya , Chang Yuqian , Lee Eunice Y. , Wang Eddy Hsi Chun , Christiano Angela M.
Published: September 2022

Alopecia areata (AA) is an autoimmune disease caused by T cell-mediated destruction of the hair follicle (HF). Therefore, approaches that effectively disrupt pathogenic T cell responses are predicted to have therapeutic benefit for AA treatment. T cells rely on the duality of T cell receptor (TCR) and gamma chain (γc) cytokine signaling for their development, activation, and peripheral homeostasis. Ifidancitinib is a potent and selective next-generation JAK1/3 inhibitor predicted to disrupt γc cytokine signaling. We found that Ifidancitinib robustly induced hair regrowth in AA-affected C3H/HeJ mice when fed with Ifidancitinib in chow diets. Skin taken from Ifidancitinib-treated mice showed significantly decreased AA-associated inflammation. CD44+CD62L- CD8+ T effector/memory cells, which are associated with the pathogenesis of AA, were significantly decreased in the peripheral lymphoid organs in Ifidancitinib-treated mice. We observed high expression of co-inhibitory receptors PD-1 on effector/memory CD8+ T cells, together with decreased IFN-γ production in Ifidancitinib-treated mice. Furthermore, we found that γc cytokines regulated T cell exhaustion. Taken together, our data indicate that selective induction of T cell exhaustion using a JAK inhibitor may offer a mechanistic explanation for the success of this treatment strategy in the reversal of autoimmune diseases such as AA.
P2Y6 receptor-mediated signaling amplifies TLR-induced pro-inflammatory responses in microglia
Authors: Timmerman Raissa , Zuiderwijk-Sick Ella A. , Bajramovic Jeffrey J.
Published: September 2022

TLR-induced signaling initiates inflammatory responses in cells of the innate immune system. These responses are amongst others characterized by the secretion of high levels of pro-inflammatory cytokines, which are tightly regulated and adapted to the microenvironment. Purinergic receptors are powerful modulators of TLR-induced responses, and we here characterized the effects of P2Y6 receptor (P2RY6)-mediated signaling on TLR responses of rhesus macaque primary bone marrow-derived macrophages (BMDM) and microglia, using the selective P2RY6 antagonist MRS2578. We demonstrate that P2RY6-mediated signaling enhances the levels of TLR-induced pro-inflammatory cytokines in microglia in particular. TLR1, 2, 4, 5 and 8-induced responses were all enhanced in microglia, whereas such effects were much less pronounced in BMDM from the same donors. Transcriptome analysis revealed that the overall contribution of P2RY6-mediated signaling to TLR-induced responses in microglia leads to an amplification of pro-inflammatory responses. Detailed target gene analysis predicts that P2RY6-mediated signaling regulates the expression of these genes via modulation of the activity of transcription factors NFAT, IRF and NF-κB. Interestingly, we found that the expression levels of heat shock proteins were strongly induced by inhibition of P2RY6-mediated signaling, both under homeostatic conditions as well as after TLR engagement. Together, our results shed new lights on the specific pro-inflammatory contribution of P2RY6-mediated signaling in neuroinflammation, which might open novel avenues to control brain inflammatory responses.
Detection of rare autoreactive T cell subsets in patients with pemphigus vulgaris
Authors: Polakova Alexandra , Kauter Leonie , Ismagambetova Adina , Didona Dario , Solimani Farzan , Ghoreschi Kamran , Hertl Michael , Möbs Christian , Hudemann Christoph
Published: September 2022

Analysis of T lymphocyte proliferation and activation after antigenic or mitogenic stimulation is a vital parameter used in the diagnosis of various immuno-deficiencies and during the monitoring of treatment responses. Most applied techniques are based on the incorporation of tritiated thymidine (3H-TdR) or ELISPOT analysis, both rely on rather time-consuming/-intensiveex vivoprotocols or encompass inherent drawbacks such as the inability to distinguish specific cell populations (3H-TdR, ELISPOT) or focus on a single cytokine (ELISPOT). Here we aimed at characterizing the rapid expression of intracellular CD154 (CD40L) as a marker for rare antigen-specific CD4+ T cells in pemphigus vulgaris (PV). Upon stimulation with human desmoglein (Dsg) 3, the major autoantigen in PV, the expression of CD154 was significantly increased in PV patients compared to healthy controls (HC) and correlated with anti-Dsg3 IgG titers. Patients with active disease showed higher numbers of Dsg3-reactive CD4+ T cells in CXCR5+ T follicular helper cells. In remittent PV and HC, CXCR5+CD4+ T cells remained largely unaffected by Dsg3. IL-17 and IL-21 expression were significantly induced only in CD154+CD4+ T cells from PV patients, lending themselves as potential novel treatment targets. Additionally, stimulation with immunodominant Dsg3-derived epitopes strongly induced a CD4+ T cell responseviaCD40-CD154 interaction similar to the human Dsg3 protein. We here established a rapidex vivoassay allowing the detection of Dsg3-reactive CD4+ T cells from activated systemically available PBMCs, which further supports the crucial concept of antigen-specific T cells in the pathogenesis of PV.
A rapid turnaround gene panel for severe autoinflammation: Genetic results within 48 hours
Authors: McCreary Dara , Omoyinmi Ebun , Hong Ying , Jensen Barbara , Burleigh Alice , Price-Kuehne Fiona , Gilmour Kimberly , Eleftheriou Despina , Brogan Paul
Published: September 2022

There is an important unmet clinical need for fast turnaround next generation sequencing (NGS) to aid genetic diagnosis of patients with acute and sometimes catastrophic inflammatory presentations. This is imperative for patients who require precise and targeted treatment to prevent irreparable organ damage or even death. Acute and severe hyper- inflammation may be caused by primary immunodeficiency (PID) with immune dysregulation, or more typical autoinflammatory diseases in the absence of obvious immunodeficiency. Infectious triggers may be present in either immunodeficiency or autoinflammation. We compiled a list of 25 genes causing monogenetic immunological diseases that are notorious for their acute first presentation with fulminant inflammation and which may be amenable to specific treatment, including hemophagocytic lymphohistiocytosis (HLH); and autoinflammatory diseases that can present with early-onset stroke or other irreversible neurological inflammatory complications. We designed and validated a pipeline that enabled return of clinically actionable results in hours rather than weeks: the Rapid Autoinflammation Panel (RAP). We demonstrated accuracy of this new pipeline, with 100% sensitivity and 100% specificity. Return of results to clinicians was achieved within 48-hours from receiving the patient’s blood or saliva sample. This approach demonstrates the potential significant diagnostic impact of NGS in acute medicine to facilitate precision medicine and save “life or limb” in these critical situations.
Impact of a sensory stimulation program conducted by family members on the consciousness and pain levels of ICU patients: A mixed method study
Authors: Adineh Mohammad , Elahi Nasrin , Molavynejad Shahram , Jahani Simin , Savaie Mohsen
Published: September 2022

Background

The results of several studies show the different effects of a balanced sensory stimulation program (SSP) on patients with brain injury admitted to the intensive care unit (ICU), but these effects have been less studied based on mixed and comprehensive methods.

Method

This mixed-method study involved 66 patients with brain injury admitted to the ICU who were allocated into intervention (n= 33) and control (n= 33) groups using random stratified sampling. Patients in the intervention group received a sensory stimulation program from family members for 1 h daily during ICU hospitalization, while the control group received only routine care. Patients' level of consciousness and pain intensity were measured immediately before and after the intervention using Glasgow Coma Scale (GCS) and Behavioral Pain Scale (BPS), respectively. In-depth unstructured interviews were conducted with the patients in the intervention group 3 months after discharge from the ICU. These interviews were analyzed following Graneheim and Lundman (2004) conventional content analysis method.

Results

A significant difference was found between the study groups in terms of the mean difference of GCS (P=0.001) and BPS score (P= 0.001) before and after intervention. Patients in the intervention group had a higher mean GCS and a lower mean BPS than did patients in the control group. The main themes extracted from the qualitative analysis confirmed the results obtained from the quantitative phase of the study.

Conclusion

The combination of the quantitative and qualitative findings suggested that amidst the many hardships and sufferings brain injury patients go through in the ICU, a sensory stimulation program offered by family members may have many benefits such as increased level of consciousness and reduced pain for these patients. Therefore, it is necessary to formulate a framework for this program and provide the needed facilities in order to benefit more from the capacity of such programs for ICU patients.
Influence of plant genotype and soil on the cotton rhizosphere microbiome
Authors: Yang Chuanzhen , Yue Hongchen , Ma Zheng , Feng Zili , Feng Hongjie , Zhao Lihong , Zhang Yalin , Deakin Greg , Xu Xiangming , Zhu Heqin , Wei Feng
Published: September 2022

Rhizosphere microbial communities are recognized as crucial products of intimate interactions between plant and soil, playing important roles in plant growth and health. Enhancing the understanding of this process is a promising way to promote the next green revolution by applying the multifunctional benefits coming with rhizosphere microbiomes. In this study, we propagated eight cotton genotypes (four upland cotton cultivars and four sea-land cotton cultivars) with varying levels of resistance to Verticillium dahliae in three distinct soil types. Amplicon sequencing was applied to profile both bacterial and fungal communities in the rhizosphere of cotton. The results revealed that soil origin was the primary factor causing divergence in rhizosphere microbial community, with plant genotype playing a secondary role. The Shannon and Simpson indices revealed no significant differences in the rhizosphere microbial communities of Gossypium barbadense and G. hirsutum. Soil origin accounted for 34.0 and 59.05% of the total variability in the PCA of the rhizosphere bacterial and fungal communities, respectively, while plant genotypes within species only accounted for 1.1 to 6.6% of the total variability among microbial population. Similar results were observed in the Bray–Curtis indices. Interestingly, the relative abundance of Acidobacteria phylum in G. barbadense was greater in comparison with that of G. hirsutum. These findings suggested that soil origin and cotton genotype modulated microbiome assembly with soil predominantly shaping rhizosphere microbiome assembly, while host genotype slightly tuned this recruitment process by changing the abundance of specific microbial consortia.
Comparative transcriptomic and lipidomic analyses indicate that cold stress enhanced the production of the long C18–C22 polyunsaturated fatty acids in Aurantiochytrium sp.
Authors: Song Yingjie , Hu Zhangli , Xiong Zheng , Li Shuangfei , Liu Wei , Tian Tian , Yang Xuewei
Published: September 2022

Aurantiochytrium sp. belonging to Thraustochytrids are known for their capacity to produce long-chain polyunsaturated fatty acids (PUFAs). However, effects of cold stress accompanied with staged-temperature control on the fatty acid metabolism in Aurantiochytrium sp. were rarely studied. In this study, cold stress (15°C, 5°C) was applied for Aurantiochytrium sp., with the physiological responses (morphology, growth, fatty acid profiling) and gene expression related FA synthesis, lipid metabolism, and regulatory processes was observed. Results showed that there is a significant change for the lipid types under 5°C (251 species) and 15°C (97 species) treatment. The 5°C treatment was benefit for the C18–C22 PUFAs with the yield of docosahexaenoic acid (DHA) increased to 1.25 times. After incubation at 15°C, the accumulation of eicosadienoic acid (EA) (20:2) was increased to 2.00-fold. Based on transcriptomic and qPCR analysis, an increase in genes involved in fatty acid synthase (FAS) and polyketide synthase (PKS) pathways was observed under low-temperature treatment. With upregulation of 3-ketoacyl-CoA synthase (2.44-fold), ketoreductase (2.50-fold), and dTDP-glucose 4,6-Dehydratase (rfbB) (2.31-fold) involved in PKS pathway, the accumulation of DHA was enhanced under 5°C. While, FAS and fatty elongase 3 (ELO) involved in the FAS pathway were upregulated (1.55-fold and 2.45-fold, respectively) to accumulate PUFAs at 15°C. Additionally, glycerol-3-phosphate acyltransferase (GPAT), lysophospholipid acyltransferase (LPAT), phosphatidic acid phosphatase (PAP), phosphatidylserine synthase (PSS), and phosphatidylserine decarboxylase (PSD) involved in glycerophospholipid biosynthesis were upregulated at 5°C increasing the accumulation of phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and phosphatidylinositol (PI). However, glycolysis and the TCA cycle were inhibited under 5°C. This study provides a contribution to the application of two-staged temperature control in the Aurantiochytrium sp. fermentation for producing cold stress-enhancing PUFAs, in order to better understand the function of the key genes for future genetic engineering.
Regulation of the cecal microbiota community and the fatty liver deposition by the addition of brewers’ spent grain to feed of Landes geese
Authors: Xu Ping , Hong Yuxuan , Chen Pinpin , Wang Xu , Li Shijie , Wang Jie , Meng Fancong , Zhou Zutao , Shi Deshi , Li Zili , Cao Shengbo , Xiao Yuncai
Published: September 2022

The effects of brewers’ spent grain (BSG) diets on the fatty liver deposition and the cecal microbial community were investigated in a total of 320 healthy 5-day-old Landes geese. These geese were randomly and evenly divided into 4 groups each containing 8 replicates and 10 geese per replicate. These four groups of geese were fed from the rearing stage (days 5–60) to the overfeeding stage (days 61–90). The Landes geese in group C (control) were fed with basal diet (days 5–90); group B fed first with basal diet in the rearing stage and then basal diet + 4% BSG in the overfeeding stage; group F first with basal diet + 4% BSG during the rearing stage and then basal diet in the overfeeding stage; and group W with basal diet + 4% BSG (days 5–90). The results showed that during the rearing stage, the body weight (BW) and the average daily gain (ADG) of Landes geese were significantly increased in groups F and W, while during the overfeeding stage, the liver weights of groups W and B were significantly higher than that of group C. The taxonomic structure of the intestinal microbiota revealed that during the overfeeding period, the relative abundance of Bacteroides in group W was increased compared to group C, while the relative abundances of Escherichia–Shigella and prevotellaceae_Ga6A1_group were decreased. Results of the transcriptomics analysis showed that addition of BSG to Landes geese diets altered the expression of genes involved in PI3K-Akt signaling pathway and sphingolipid metabolism in the liver. Our study provided novel experimental evidence based on the cecal microbiota to support the application of BSG in the regulation of fatty liver deposition by modulating the gut microbiota in Landes geese.
Resistance and virulence features of hypermucoviscous Klebsiella pneumoniae from bloodstream infections: Results of a nationwide Italian surveillance study
Authors: Arena Fabio , Menchinelli Giulia , Di Pilato Vincenzo , Torelli Riccardo , Antonelli Alberto , Henrici De Angelis Lucia , Coppi Marco , Sanguinetti Maurizio , Rossolini Gian Maria
Published: September 2022

Among Enterobacterales, Klebsiella pneumoniae (Kp) is one of the major opportunistic pathogens causing hospital-acquired infections. The most problematic phenomenon linked to Kp is related to the dissemination of multi-drug resistant (MDR) clones producing carbapenem-hydrolyzing enzymes, representing a clinical and public health threat at a global scale. Over the past decades, high-risk MDR clones (e.g., ST512, ST307, ST101 producing blaKPC–type carbepenemases) have become endemic in several countries, including Italy. Concurrently, the spread of highly virulent Kp lineages (e.g., ST23, ST86) able to cause severe, community-acquired, pyogenic infections with metastatic dissemination in immunocompetent subjects has started to be documented. These clones, designated as hypervirulent Kp (hvKp), produce an extensive array of virulence factors and are highly virulent in previously validated animal models. While the prevalence and distribution of MDR Kp has been previously assessed at local and national level knowledge about dissemination of hvKp remains scarce. In this work, we studied the phenotypic and genotypic features of hypermucoviscous (HMV, as possible marker of increased virulence) Kp isolates from bloodstream infections (BSI), obtained in 2016–17 from 43 Italian Laboratories. Antimicrobial susceptibility testing, whole genome sequencing and the use of two animal models (G. mellonella and murine) were employed to characterize collected isolates. Over 1502 BSI recorded in the study period, a total of 19 Kp were selected for further investigation based on their HMV phenotype. Results showed that hvKp isolates (ST5, ST8, ST11, ST25) are circulating in Italy, although with a low prevalence and in absence of a clonal expansion; convergence of virulence (yersiniabactin and/or salmochelin, aerobactin, regulators of mucoid phenotype) and antimicrobial-resistance (extended-spectrum beta-lactamases) features was observed in some cases. Conventional MDR Kp clones (ST307, ST512) may exhibit an HMV phenotype, but with a low virulence potential in the animal models. To the best of our knowledge, this work represents the first systematic survey on HMV and hvKp in Italy, employing a functional characterization of collected isolates. Future surveillance programs are warranted to monitor the threatening convergence of virulence and resistance among MDR Kp and the spread of hvKp.
Controlled human infectious models, a path forward in uncovering immunological correlates of protection: Lessons from enteric fevers studies
Authors: Sztein Marcelo B. , Booth Jayaum S.
Published: September 2022

Enteric infectious diseases account for more than a billion disease episodes yearly worldwide resulting in approximately 2 million deaths, with children under 5 years old and the elderly being disproportionally affected. Enteric pathogens comprise viruses, parasites, and bacteria; the latter including pathogens such asSalmonella[typhoidal (TS) and non-typhoidal (nTS)], cholera,Shigellaand multiple pathotypes ofEscherichia coli(E. coli). In addition, multi-drug resistant and extensively drug-resistant (XDR) strains (e.g.,S.Typhi H58 strain) of enteric bacteria are emerging; thus, renewed efforts to tackle enteric diseases are required. Many of these entero-pathogens could be controlled by oral or parenteral vaccines; however, development of new, effective vaccines has been hampered by lack of known immunological correlates of protection (CoP) and limited knowledge of the factors contributing to protective responses. To fully comprehend the human response to enteric infections, an invaluable tool that has recently re-emerged is the use of controlled human infection models (CHIMs) in which participants are challenged with virulent wild-type (wt) organisms. CHIMs have the potential to uncover immune mechanisms and identify CoP to enteric pathogens, as well as to evaluate the efficacy of therapeutics and vaccines in humans. CHIMs have been used to provide invaluable insights in the pathogenesis, host-pathogen interaction and evaluation of vaccines. Recently, several Oxford typhoid CHIM studies have been performed to assess the role of multiple cell types (B cells, CD8+ T, Tregs, MAIT, Monocytes and DC) duringS. Typhi infection. One of the key messages that emerged from these studies is that baseline antigen-specific responses are important in that they can correlate with clinical outcomes. Additionally, volunteers who develop typhoid disease (TD) exhibit higher levels and more activated cell types (e.g., DC and monocytes) which are nevertheless defective in discrete signaling pathways. Future critical aspects of this research will involve the study of immune responses to enteric infections at the site of entry, i.e., the intestinal mucosa. This review will describe our current knowledge of immunity to enteric feverscaused byS.Typhi andS.Paratyphi A, with emphasis on the contributions of CHIMs to uncover the complex immunological responses to these organisms and provide insights into the determinants of protective immunity.
Treatments for kinesiophobia in people with chronic pain: A scoping review
Authors: Bordeleau Martine , Vincenot Matthieu , Lefevre Salomé , Duport Arnaud , Seggio Lucas , Breton Tomy , Lelard Thierry , Serra Eric , Roussel Nathalie , Neves Jeremy Fonseca Das , Léonard Guillaume
Published: September 2022

Kinesiophobia is associated with pain intensity in people suffering from chronic pain. The number of publications highlighting this relationship has increased significantly in recent years, emphasizing the importance of investigating and synthesizing research evidence on this topic. The purpose of this scoping review was to answer the following questions: (1) What types of interventions have been or are currently being studied in randomized controlled trials (RCTs) for the management of kinesiophobia in patients with chronic pain? (2) What chronic pain conditions are targeted by these interventions? (3) What assessment tools for kinesiophobia are used in these interventions? According to the studies reviewed, (1) physical exercise is the most commonly used approach for managing irrational fear of movement, (2) interventions for kinesiophobia have primarily focused on musculoskeletal pain conditions, particularly low back pain and neck pain, and (3) the Tampa Scale of Kinesiophobia is the most commonly used tool for measuring kinesiophobia. Future RCTs should consider multidisciplinary interventions that can help patients confront their irrational fear of movement while taking into account the patient’s personal biological, psychological, and social experiences with pain and kinesiophobia.
Chronic, but not sub-chronic, stress increases binge-like alcohol consumption in male and female c57BL6 mice
Authors: McCarthy William , Huq Shama N. , Allen Kristen , Scally Lindsay , Petri Avelina , Wujek Madeline , Sachs Benjamin D.
Published: September 2022

Stress is known to contribute to mental illness and alcohol use disorders, which are highly prevalent and lead to considerable disability. These stress-related disorders are characterized by significant sex differences, which remain poorly understood. Preclinical research comparing the effects of stress in males and females has the potential to provide new insights into the neurobiology of these conditions. The current study compared the effects of chronic and sub-chronic exposure to variable environmental stressors on binge-like alcohol consumption using the drinking-in-the-dark model in male and female c57BL6 mice. The results reveal that chronic, but not sub-chronic, exposure to variable stress increases alcohol intake in both sexes. Stress-induced alterations in gene expression were also compared in the nucleus accumbens, a brain region widely known to play a key role in stress susceptibility and reward processing. Real-time PCR data indicate that chronic, but not sub-chronic, environmental stress leads to downregulation of adenosine 2A (A2A) receptor mRNA. By contrast, sub-chronic stress increased CREB expression, while chronic stress did not. Several sex differences in the effects of stress on gene expression were also noted. Our results demonstrate that reductions in A2A receptor mRNA in the nucleus accumbens are associated with the increased binge drinking of chronically stressed animals, but future work will be required to determine the functional importance of this gene expression change. Continuing to define the molecular alterations associated with stress-induced increases in alcohol intake has the potential to provide insights into the development and progression of stress-related disorders.