bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental validation of finite element simulation of a new custom-designed fixation plate to treat mandibular angle fracture
Authors: Xu Xu , Cheng Kang-jie , Liu Yun-feng , Fan Ying-ying , Wang Joanne H. , Wang Russell , Baur Dale A. , Jiang Xian-feng , Dong Xing-tao
Published: February 2021

Background

The objective of the study was to validate biomechanical characteristics of a 3D-printed, novel-designated fixation plate for treating mandibular angle fracture, and compare it with two commonly used fixation plates by finite element (FE) simulations and experimental testing.

Methods

A 3D virtual mandible was created from a patient’s CT images as the master model. A custom-designed plate and two commonly used fixation plates were reconstructed onto the master model for FE simulations. Modeling of angle fracture, simulation of muscles of mastication, and defining of boundary conditions were integrated into the theoretical model. Strain levels during different loading conditions were analyzed using a finite element method (FEM). For mechanical test design, samples of the virtual mandible with angle fracture and the custom-designed fixation plates were printed using selective laser sintering (SLS) and selective laser melting (SLM) printing methods. Experimental data were collected from a testing platform with attached strain gauges to the mandible and the plates at different 10 locations during mechanical tests. Simulation of muscle forces and temporomandibular joint conditions were built into the physical models to improve the accuracy of clinical conditions. The experimental vs the theoretical data collected at the 10 locations were compared, and the correlation coefficient was calculated.

Results

The results show that use of the novel-designated fixation plate has significant mechanical advantages compared to the two commonly used fixation plates. The results of measured strains at each location show a very high correlation between the physical model and the virtual mandible of their biomechanical behaviors under simulated occlusal loading conditions when treating angle fracture of the mandible.

Conclusions

Based on the results from our study, we validate the accuracy of our computational model which allows us to use it for future clinical applications under more sophisticated biomechanical simulations and testing.
Unpacking power dynamics in research and evaluation on social accountability for sexual and reproductive health and rights
Authors: Schaaf Marta , Cant Suzanne , Cordero Joanna , Contractor Sana , Wako Etobssie , Marston Cicely
Published: February 2021

Over the past decade, social accountability for health has coalesced into a distinct field of research and practice. Whether explicitly stated or not, changed power relations are at the heart of what social accountability practitioners seek, particularly in the context of sexual and reproductive health. Yet, evaluations of social accountability programs frequently fail to assess important power dynamics. In this commentary, we argue that we must include an examination of power in research and evaluation of social accountability in sexual and reproductive health, and suggest ways to do this. The authors are part of a community of practice on measuring social accountability and health outcomes. We share key lessons from our efforts to conduct power sensitive research using different approaches and methods.

First, participatory research and evaluation approaches create space for program participants to engage actively in evaluations by defining success. Participation is also one of the key elements of feminist evaluation, which centers power relations rooted in gender. Participatory approaches can strengthen ‘traditional’ health evaluation approaches by ensuring that the changes assessed are meaningful to communities.

Fields from outside health offer approaches that help to describe and assess changes in power dynamics. For example, realist evaluation analyses the causal processes, or mechanisms, grounded in the interactions between social, political and other structures and human agency; programs try to influence these structures and/or human agency. Process tracing requires describing the mechanisms underlying change in power dymanics in a very detailed way, promoting insight into how changes in power relationships are related to the broader program.

Finally, case aggregation and comparison entail the aggregation of data from multiple cases to refine theories about when and how programs work. Case aggregation can allow for nuanced attention to context while still producing lessons that are applicable to inform programming more broadly.

We hope this brief discussion encourages other researchers and evaluators to share experiences of analysing power relations as part of evaluation of social accountability interventions for sexual and reproductive health so that together, we improve methodology in this crucial area.
Selective treatment pressure in colon cancer drives the molecular profile of resistant circulating tumor cell clones
Authors: Cayrefourcq Laure , Thomas Frédéric , Mazard Thibault , Assenat Eric , Assou Said , Alix-Panabières Catherine
Published: February 2021

The characterization of circulating tumor cells (CTCs) holds promises for precision medicine because these cells are an important clinical indicator of treatment efficacy. We established the first and still only nine permanent colon CTC lines from peripheral blood samples of a patient with metastatic colon cancer collected at different time points during treatment and cancer progression. The study objectives were (i) to compare the gene expression profiles of these CTC lines, and (ii) to determine the main features acquired during treatment. The number of upregulated genes was higher in the CTC lines obtained after treatment, indicating that they acquired properties to escape treatment pressure. Among these upregulated genes, some are involved in the mTOR and PI3K/AKT signaling pathways. Moreover, cytidine deaminase expression was significantly increased in the CTC lines obtained after failure of the first- and second-line 5-fluorouracile-based treatments, suggesting that these CTCs can eliminate this specific drug and resist to therapy. Several enzymes involved in xenobiotic metabolism also were upregulated after treatment, suggesting the activation of detoxification mechanisms in response to chemotherapy. Finally, the significant higher expression of aldolase B in four of the six CTC lines obtained after treatment withdrawal and cancer progression indicated that these clones originated from liver metastases. In conclusion, these CTC lines generated at different time points during treatment of metastatic colon cancer in a single patient are characterized by the deregulation of different genes that promote (i) drug resistance, (ii) xenobiotic and energy metabolism, and (iii) stem cell properties and plasticity.
Translation and cross-cultural adaptation of WHOQOL-HIV Bref among people living with HIV/AIDS in Pakistan
Authors: Ahmed Ali , Saqlain Muhammad , Akhtar Nasim , Hashmi Furqan , Blebil Ali , Dujaili Juman , Umair Malik Muhammad , Bukhsh Allah
Published: February 2021

Background

Reliable Health-Related Quality of Life (HRQoL) assessment will be useful in identifying health issues and in identifying health care actions. Due to the lack of a psychometrically valid tool in Urdu, we aim to translate and examine the psychometric and cross-cultural adaptation of WHOQOL HIV Bref among people living with HIV/AIDS (PLWHA) in Pakistan.

Methods

The standard forward-backwards translation technique was used to convert English version of the WHOQOL HIV Bref into Urdu. After cognitive debriefing, final Urdu version of instrument was developed. Based on the principle of at least 5 subjects for each item, a sample of 182 patients was used using a universal random sampling technique from the Pakistan Institute of Medical Sciences, Islamabad. The Cronbach’s alpha and intra-class correlation coefficients (ICC) were estimated to assess internal validity and reliability of the translated version. Exploratory factor analysis was carried out to determine the factor structure and independent associations between the instrument domains and CD-4T-cell count were assessed using multivariable linear regression

Results

High Cronbach alpha 0.93 was found for all WHOQOL HIV Bref facets. The test–retest reliability demonstrated a statistically significant ICC ranged from 0.88 to 0.98 (p < 0.001). In known group validity, lower CD-4 lymphocytes count was significantly related to poor scores for all six domains (p < 0.001). Similarly, symptomatic subjects had significantly lower scores compared to asymptomatic subjects on the physical, psychological, social relationship and independence domains (p < 0.05). Statistically significant positive correlation of all six domains of instrument with CD4 cells count (p < 0.001), exhibiting patients with higher CD-4 cells will have higher mean scores of all domains. Factor analysis revealed 5 domains, including physical health, psychological health, social relationship, environmental, and spiritual health. Multivariable linear regression analysis reported; only physical, psychological health and environment health domains were found significantly associated with higher CD-4 lymphocytes count (Beta = 0.121, p < 0.001, Beta = 0.103, p = 0.002, and Beta = 0.032, p = 0.032).

Conclusion

Findings suggested that the Urdu version of WHOQOL HIV Bref is a psychometrically valid and culturally well-adapted HRQoL measurement tool for PLWHA in Pakistan.
Association of ABO blood groups with ovarian reserve, and outcomes after assisted reproductive technology: systematic review and meta-analyses
Authors: Zhao Jing , Yao Zhongyuan , Hao Jie , Xu Bin , Wang Yonggang , Li Yanping
Published: February 2021

Background

There has been an interest in the relationship between ABO blood groups and infertility. Many studies have investigated the association of ABO blood groups with diminished ovarian reserve (DOR), ovarian hyperstimulation syndrome (OHSS), and outcomes of assisted reproductive technology (ART), with controversial results.

Methods

A systematic review and meta-analysis was conducted to evaluating the association of ABO blood groups with DOR, OHSS, and outcomes of ART.

Results

Thirteen studies performed between 2010 and 2018 were included in this meta-analysis. DOR, OHSS, live birth rate (LBR), clinical pregnancy rate (CPR), miscarriage rate (MR) were reported in 9, 2, 4, 3, 2 studies, respectively. The combined results showed similar risk of DOR among individuals with blood group A (RR, 0.98; 95% confidence interval [CI], 0.85, 1.13), B (RR, 0.96; 95% CI, 0.76, 1.20), AB (RR, 1.00; 95% CI, 0.76, 1.30), and non-O (RR, 0.94; 95% CI, 0.79, 1.11) as compared to those with blood group O. Meta-analysis showed that the incidences of OHSS were similar in women with blood group A (RR, 1.05; 95% CI, 0.66, 1.66), B (RR, 1.04; 95% CI, 0.46, 2.35), AB (RR, 0.51; 95% CI, 0.10, 2.56), non-O (RR, 1.02; 95% CI, 0.65, 1.57) with blood group O. As to the clinical outcomes, meta-analysis showed no difference in LBR among individuals with blood group A (RR, 1.27; 95% CI, 0.74, 2.17), B (RR, 1.47; 95% CI, 0.95, 2.29), AB (RR, 1.48; 95% CI, 0.76, 2.90), non-O (RR, 1.28; 95% CI, 0.83, 1.98) when compared to those with blood group O. Similarly, the results also found that there were no difference in CPR and MR between women with blood A (CPR: RR, 1.12), B (CPR: RR, 1.08), AB (CPR: RR, 1.05), non-O (CPR: RR, 1.05; MR: RR, 0.94) and blood group O.

Conclusions

ABO blood groups may not be associated with DOR, OHSS, LBR, CPR, and MR of ART. Infertility and ART outcomes are influenced by multiple factors. Blood groups should not be taken into account excessively during diagnosis and treatment of infertile women.
Computer-aided design of PVR mutants with enhanced binding affinity to TIGIT
Authors: Zhou Xiaowen , Du Jiangfeng , Zhou Xiuman , Niu Xiaoshuang , Li Wanqiong , Chen Chunxia , Lv Sifan , Wu Aijun , Gou Shanshan , Sun Yixuan , Zhai Wenjie , Qiu Lu , Qi Yuanming , Zhao Wenshan , Gao Yanfeng
Published: February 2021

Background

TIGIT, as a novel immune checkpoint molecule involved in T cell and NK cell anergy, could induce the immune tolerance and escape through binding with its ligand PVR. Blockade of TIGIT/PVR is considered as a promising strategy in cancer immunotherapy. However, to facilitate the design of inhibitors targeting TIGIT/PVR, the structural characteristics and binding mechanism still need to be further studied.

Methods

In this study, molecular dynamics (MD) simulations and in silico mutagenesis were used to analyze the interaction between TIGIT and its ligand PVR. Then, PVR mutants were designed and their activities were determined by using TIGIT overexpressed Jurkat cells.

Results

The results suggested that the loops of PVR (CC′ loop, C′C″ loop, and FG loop) underwent a large intra-molecular rearrangement, and more hydrogen bond crosslinking between PVR and TIGIT were formed during MD simulations. The potential residues for PVR to interact with TIGIT were identified and utilized to predict high affinity PVR mutants. Through the biological activity evaluation, four PVR mutants (PVRS72W, PVRS72R, PVRG131V and PVRS132Q) with enhanced affinity to TIGIT were discovered, which could elicit more potent inhibitory effects compared with the wild type PVR.

Conclusions

The MD simulations analysis provided new insights into the TIGIT/PVR interaction model, and the identified PVR mutants (PVRS72W, PVRS72R, PVRG131V and PVRS132Q) could serve as new candidates for immunotherapy to block TIGIT/PVR.
Transfer of rhodamine-123 into the brain and cerebrospinal fluid of fetal, neonatal and adult rats
Authors: Koehn Liam M. , Dziegielewska Katarzyna M. , Habgood Mark D. , Huang Yifan , Saunders Norman R.
Published: February 2021

Background

Adenosine triphosphate binding cassette transporters such as P-glycoprotein (PGP) play an important role in drug pharmacokinetics by actively effluxing their substrates at barrier interfaces, including the blood-brain, blood-cerebrospinal fluid (CSF) and placental barriers. For a molecule to access the brain during fetal stages it must bypass efflux transporters at both the placental barrier and brain barriers themselves. Following birth, placental protection is no longer present and brain barriers remain the major line of defense. Understanding developmental differences that exist in the transfer of PGP substrates into the brain is important for ensuring that medication regimes are safe and appropriate for all patients.

Methods

In the present study PGP substrate rhodamine-123 (R123) was injected intraperitoneally into E19 dams, postnatal (P4, P14) and adult rats. Naturally fluorescent properties of R123 were utilized to measure its concentration in blood-plasma, CSF and brain by spectrofluorimetry (Clariostar). Statistical differences in R123 transfer (concentration ratios between tissue and plasma ratios) were determined using Kruskal-Wallis tests with Dunn’s corrections.

Results

Following maternal injection the transfer of R123 across the E19 placenta from maternal blood to fetal blood was around 20 %. Of the R123 that reached fetal circulation 43 % transferred into brain and 38 % into CSF. The transfer of R123 from blood to brain and CSF was lower in postnatal pups and decreased with age (brain: 43 % at P4, 22 % at P14 and 9 % in adults; CSF: 8 % at P4, 8 % at P14 and 1 % in adults). Transfer from maternal blood across placental and brain barriers into fetal brain was approximately 9 %, similar to the transfer across adult blood-brain barriers (also 9 %). Following birth when placental protection was no longer present, transfer of R123 from blood into the newborn brain was significantly higher than into adult brain (3 fold, p < 0.05).

Conclusions

Administration of a PGP substrate to infant rats resulted in a higher transfer into the brain than equivalent doses at later stages of life or equivalent maternal doses during gestation. Toxicological testing of PGP substrate drugs should consider the possibility of these patient specific differences in safety analysis.
Role of patients associations in connective tissue calcifiying diseases: a position statement from EuroSoftCalc.Net group
Authors: Valdivielso Pedro , Jacinto Marta , Devernois Guillemette , Laplana Jorge , García-Fernández Maria , Martin Ludovic
Published: February 2021

Patients have been showing a growing interest in taking active participation in decision making, and having the opportunity to drive clinical investigation. This is more common for patients who have a rare disease than for those with more prevalent diseases. The EuroSoftCalc.Net COST Action, a group of clinicians and researchers involved in the dystrophic calcification process held a meeting in which three representatives of patients’ associations, coming from Portugal, France and Spain, discussed the role of patients and their associations, namely in the Action, and also the main concerns in their countries. The disparities in health care between European Union countries with regard to connective tissue calcifying diseases, and the existing conflicts of interest, were a matter of debate during the meeting. As a consequence of the presentations and the debate that followed, it became clear that, despite their countries, the main concerns of the patients are identical, namely a lack of specific therapy and follow-up clinical guidelines, delays in the diagnosis, difficulties in getting members to enrol to associations, and/or difficulties with doctors’ explanations for the diseases. The attendees also agreed that EuroSoftCalc.Net group should help to set up new associations where no Patient Associations presently exist, and, furthermore, should release diagnosis and follow-up guidelines, especially helpful in countries, and/or for diseases, where no multidisciplinary consultations are available.
COVID-19 and cytokine storm syndrome: can what we know about interleukin-6 in ovarian cancer be applied?
Authors: Macciò Antonio , Oppi Sara , Madeddu Clelia
Published: February 2021

Improving early diagnosis along with timely and effective treatment of COVID-19 are urgently needed. However, at present, the mechanisms underlying disease spread and development, defined prognosis, and immune status of patients with COVID-19 remain to be determined. Patients with severe disease state exhibit a hyperinflammatory response associated with cytokine storm syndrome, hypercoagulability, and depressed cell-mediated immunity. These clinical manifestations, sharing similar pathogenesis, have been well-studied in patients with advanced ovarian cancer. The present review suggests treatment approaches for COVID-19 based on strategies used against ovarian cancer, which shares similar immunopathology and associated coagulation disorders.

The chronicization of the hyperinflammatory cytokine storm in patients with severe COVID-19 highlights a defective resistance phase that leads to aspecific chronic inflammation, associated with oxidative stress, which impairs specific T-cell response, induces tissue and endothelial damage, and thrombosis associated with systemic effects that lead to severe multi-organ failure and death. These events are similar to those observed in advanced ovarian cancer which share similar pathogenesis mediated primarily by Interleukin-6, which is, as well demonstrated in ovarian cancer, the key cytokine driving the immunopathology, related systemic symptoms, and patient prognosis.

Consistent with findings in other disease models with similar immunopathology, such as advanced ovarian cancer, treatment of severe COVID-19 infection should target inflammation, oxidative stress, coagulation disorders, and immunodepression to improve patient outcome. Correctly identifying disease stages, based on available laboratory data, and developing a specific protocol for each phase is essential for effective treatment.
Establishment and validation of an RNA binding protein-associated prognostic model for ovarian cancer
Authors: He Chaofan , Huang Fuxin , Zhang Kejia , Wei Jun , Hu Ke , Liang Meng
Published: February 2021

Background

Ovarian cancer (OC) is one of the most common gynecological malignant tumors worldwide, with high mortality and a poor prognosis. As the early symptoms of malignant ovarian tumors are not obvious, the cause of the disease is still unclear, and the patients’ postoperative quality of life of decreases. Therefore, early diagnosis is a problem requiring an urgent solution.

Methods

We obtained the gene expression profiles of ovarian cancer and normal samples from TCGA and GTEx databases for differential expression analysis. From existing literature reports, we acquired the RNA-binding protein (RBP) list for the human species. Utilizing the online tool Starbase, we analyzed the interaction relationship between RBPs and their target genes and selected the modules of RBP target genes through Cytoscape. Finally, univariate and multivariate Cox regression analyses were used to determine the prognostic RBP signature.

Results

We obtained 527 differentially expressed RBPs, which were involved in many important cellular events, such as RNA splicing, the cell cycle, and so on. We predicted several target genes of RBPs, constructed the interaction network of RBPs and their target genes, and obtained many modules from the Cytoscape analysis. Functional enrichment of RBP target genes also includes these important biological processes. Through Cox regression analysis, OC prognostic RBPs were identified and a 10-RBP model constructed. Further analysis showed that the model has high accuracy and sensitivity in predicting the 3/5-year survival rate.

Conclusions

Our study identified differentially expressed RBPs and their target genes in OC, and the results promote our understanding of the molecular mechanism of ovarian cancer. The current study could develop novel biomarkers for the diagnosis, treatment, and prognosis of OC and provide new ideas and prospects for future clinical research.
Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study
Authors: Lavillegrand Jean-Rémi , Mercier-Des-Rochettes Emmanuelle , Baron Elodie , Pène Frédéric , Contou Damien , Favory Raphael , Préau Sébastien , Galbois Arnaud , Molliere Chloé , Miailhe Arnaud-Félix , Reignier Jean , Monchi Mehran , Pichereau Claire , Thietart Sara , Vieille Thibault , Piton Gael , Preda Gabriel , Abdallah Idriss , Camus Marine , Maury Eric , Guidet Bertrand , Dumas Guillaume , Ait-Oufella Hafid
Published: February 2021

Background

Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC).

Methods

Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis.

Results

Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5–11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50–147] and 19.1 µg/L [5.3–54.8]. Sixty-three percent of patients (n  = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54–0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05–1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08–1.36], by 1 mmol/L, p < 0.001), total serum bilirubin (OR 1.26 [95% CI 1.12–1.41], by 50 μmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 [95% CI 1.45–5.17], p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30–6.22], p = 0.02).

Conclusions

In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.
A novel gene selection method for gene expression data for the task of cancer type classification
Authors: ÖZCAN ŞİMŞEK N. Özlem , ÖZGÜR Arzucan , GÜRGEN Fikret
Published: February 2021

Cancer is a poligenetic disease with each cancer type having a different mutation profile. Genomic data can be utilized to detect these profiles and to diagnose and differentiate cancer types. Variant calling provide mutation information. Gene expression data reveal the altered cell behaviour. The combination of the mutation and expression information can lead to accurate discrimination of different cancer types. In this study, we utilized and transferred the information of existing mutations for a novel gene selection method for gene expression data. We tested the proposed method in order to diagnose and differentiate cancer types. It is a disease specific method as both the mutations and expressions are filtered according to the selected cancer types. Our experiment results show that the proposed gene selection method leads to similar or improved performance metrics compared to classical feature selection methods and curated gene sets.
Disruption of alpha-tubulin releases carbon catabolite repression and enhances enzyme production in Trichoderma reesei even in the presence of glucose
Authors: Shibata Nozomu , Kakeshita Hiroshi , Igarashi Kazuaki , Takimura Yasushi , Shida Yosuke , Ogasawara Wataru , Koda Tohru , Hasunuma Tomohisa , Kondo Akihiko
Published: February 2021

Background

Trichoderma reesei is a filamentous fungus that is important as an industrial producer of cellulases and hemicellulases due to its high secretion of these enzymes and outstanding performance in industrial fermenters. However, the reduction of enzyme production caused by carbon catabolite repression (CCR) has long been a problem. Disruption of a typical transcriptional regulator, Cre1, does not sufficiently suppress this reduction in the presence of glucose.

Results

We found that deletion of an α-tubulin (tubB) in T. reesei enhanced both the amount and rate of secretory protein production. Also, the tubulin-disrupted (ΔtubB) strain had high enzyme production and the same enzyme profile even if the strain was cultured in a glucose-containing medium. From transcriptome analysis, the ΔtubB strain exhibited upregulation of both cellulase and hemicellulase genes including some that were not originally induced by cellulose. Moreover, cellobiose transporter genes and the other sugar transporter genes were highly upregulated, and simultaneous uptake of glucose and cellobiose was also observed in the ΔtubB strain. These results suggested that the ΔtubB strain was released from CCR.

Conclusion

Trichoderma reesei α-tubulin is involved in the transcription of cellulase and hemicellulase genes, as well as in CCR. This is the first report of overcoming CCR by disrupting α-tubulin gene in T. reesei. The disruption of α-tubulin is a promising approach for creating next-generation enzyme-producing strains of T. reesei.
Functional analysis of novel A20 variants in patients with atypical inflammatory diseases
Authors: Kadowaki Saori , Hashimoto Kunio , Nishimura Toyoki , Kashimada Kenichi , Kadowaki Tomonori , Kawamoto Norio , Imai Kohsuke , Okada Satoshi , Kanegane Hirokazu , Ohnishi Hidenori
Published: February 2021

Background

A20 haploinsufficiency (HA20) is an early-onset autoinflammatory disease caused by mutations in theTNFAIP3gene, which encodes the protein A20. Numerous truncating mutations in theTNFAIP3gene have been reported in HA20 patients, whereas fewer missense variants have had their pathogenicity confirmed. Here, we evaluated the pathogenic significance of three previously unreported missense variants of theTNFAIP3gene in suspected cases of HA20.

Methods

We obtained the clinical features and immunological data of three patients with missense variants (Glu192Lys, Ile310Thr, and Gln709Arg) of unknown significance ofTNFAIP3. We then performed in vitro functional assays including analysis of nuclear factor (NF)-κB reporter gene activity, detection of A20 expression and phosphorylation of A20 by IκB kinase β (IKKβ), and K63-deubiquitination assay usingTNFAIP3-deficient HEK293 cells. Three known pathogenic missense mutations reported previously were also investigated.

Results

The inhibitory effect on NF-κB reporter gene activity was significantly disrupted by A20 Glu192Lys and the three known mutations. The variants Ile310Thr and Gln709Arg did not show a difference from the wild type in any of the assays performed in this study.

Conclusions

Among the three variants in theTNFAIP3gene, Glu192Lys was interpreted as being likely pathogenic, but Ile310Thr and Gln709Arg as being not pathogenic (uncertain significance and likely benign, respectively), based on the American College of Medical Genetics and Genomics standards and guidelines. Our study highlights the necessity of performing in vitro functional assays, notably, NF-κB reporter gene assay, to evaluate the pathogenicity ofTNFAIP3missense variants for the accurate diagnosis of HA20.
The Animal-foods-environment interface of Klebsiella pneumoniae in Germany: an observational study on pathogenicity, resistance development and the current situation
Authors: Wareth Gamal , Neubauer Heinrich
Published: February 2021

Klebsiella (K.) pneumoniae as a multi-drug resistant (MDR) pathogen is an emerging challenge for clinicians worldwide. Virulence factors are capsular antigens, adherence factors, the O-lipopolysaccharide, and siderophores promoting infectivity. Mechanisms of antimicrobial resistance are inactivation of compounds via enzymes, change of membrane permeability, and alteration of the target site of the antimicrobial compound. In addition to environmental resistance, K. pneumoniae can survive increasing concentrations of disinfectants, if exposed. This review describes the temporal and spatial distribution of K. pneumoniae in the past decades in Germany, with emphases on the development of resistance in the non-human columns of the One-Health concept. In general, K. pneumoniae is a neglected pathogen in veterinary and environmental health, and the risk of human infection concerning animal contact and food consumption is barely investigated. Few reports exist (n = 26) on antibiotic resistance of isolates from non-human origin. Multi-drug resistance and extended-spectrum β-lactamase (MDR-ESBL) strains also resistant to carbapenems and antibiotics of the ß-lactam group harbor blaCTX-M, blaOXA, blaTEM, blaSHV, blaCMY, and PMQR have been found in animals, foods, and the environment. Colistin resistant strains carrying the mcr-1 gene were detected in wastewater. The blaCTX-M-15 and blaOXA-48 genes are the most frequently identified AMR genes in isolates of humans and were also the most predominant ESBL-genes in samples collected from animal hosts. Several aspects of the molecular epidemiology and resistance development of K. pneumoniae in farm animal populations, wildlife, and foods need intensive research. Environmental health has to be integrated into national research plans, as a lack of data is apparent. Increasing awareness of the fact that non-human sources can act as a reservoir for this pathogen has to be raised.
Golgi-associated Rab GTPases implicated in autophagy
Authors: Lu Qingchun , Wang Po-Shun , Yang Ling
Published: February 2021

Autophagy is a conserved cellular degradation process in eukaryotes that facilitates the recycling and reutilization of damaged organelles and compartments. It plays a pivotal role in cellular homeostasis, pathophysiological processes, and diverse diseases in humans. Autophagy involves dynamic crosstalk between different stages associated with intracellular vesicle trafficking. Golgi apparatus is the central organelle involved in intracellular vesicle trafficking where Golgi-associated Rab GTPases function as important mediators. This review focuses on the recent findings that highlight Golgi-associated Rab GTPases as master regulators of autophagic flux. The scope for future research in elucidating the role and mechanism of Golgi-associated Rab GTPases in autophagy and autophagy-related diseases is discussed further.
Predictive value of plasma proenkephalin and neutrophil gelatinase-associated lipocalin in acute kidney injury and mortality in cardiogenic shock
Authors:   for the CardShock investigators, Jäntti Toni , Tarvasmäki Tuukka , Harjola Veli-Pekka , Pulkki Kari , Turkia Heidi , Sabell Tuija , Tolppanen Heli , Jurkko Raija , Hongisto Mari , Kataja Anu , Sionis Alessandro , Silva-Cardoso Jose , Banaszewski Marek , DiSomma Salvatore , Mebazaa Alexandre , Haapio Mikko , Lassus Johan
Published: February 2021

Background

Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock.

Results

P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71–150) pmol/mL and 138 (84–214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1–4.4,p = 0.03] and 2.8 [95% CI 1.2–6.5,p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%,p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK24h > 105.7 pmol/L and P-NGAL24h > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1–10.7,p < 0.001) and 5.2 (95% CI 2.8–9.8,p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock.

Conclusions

High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality.

Trial registration: NCT01374867 atwww.clinicaltrials.gov, registered 16 Jun 2011—retrospectively registered
Prediction of lameness using automatically recorded activity, behavior and production data in post-parturient Irish dairy cows
Authors: Borghart G. M. , O’Grady L. E. , Somers J. R.
Published: February 2021

Background

Although visual locomotion scoring is inexpensive and simplistic, it is also time consuming and subjective. Automated lameness detection methods have been developed to replace the visual locomotion scoring and aid in early and accurate detection. Several types of sensors are measuring traits such as activity, lying behavior or temperature. Previous studies on automatic lameness detection have been unable to achieve high accuracy in combination with practical implementation in a on farm commercial setting. The objective of our research was to develop a prediction model for lameness in dairy cattle using a combination of remote sensor technology and other animal records that will translate sensor data into easy to interpret classified locomotion information for the farmer. During an 11-month period, data from 164 Holstein-Friesian dairy cows were gathered, housed at an Irish research farm. A neck-mounted accelerometer was used to gather behavioral metrics, additional automatically recorded data consisted of milk production and live weight. Locomotion scoring data were manually recorded, using a one-to-five scale (1 = non-lame, 5 = severely lame). Locomotion scores where then used to label the cows as sound (locomotion score 1) or unsound (locomotion score ≥ 2). Four supervised classification models, using a gradient boosted decision tree machine learning algorithm, were constructed to investigate whether cows could be classified as sound or unsound. Data available for model building included behavioral metrics, milk production and animal characteristics.

Results

The resulting models were constructed using various combinations of the data sources. The accuracy of the models was then compared using confusion matrices, receiver-operator characteristic curves and calibration plots. The model which achieved the highest performance according to the accuracy measures, was the model combining all the available data, resulting in an area under the curve of 85% and a sensitivity and specificity of 78%.

Conclusion

These results show that 85% of this model’s predictions were correct in identifying cows as sound or unsound, showing that the use of a neck-mounted accelerometer, in combination with production and other animal data, has potential to replace visual locomotion scoring as lameness detection method in dairy cows.
Mapping evidence of depression in HIV-seropositive MSM in sub-Saharan Africa: a scoping review protocol
Authors: Mulqueeny Delarise M. , Nkabini Senzelokuhle M. , Pokiya Manduleli H.
Published: February 2021

Background

Depression is one of the most prevalent mental disorders among an estimated 25.6 million people living with HIV (PLHIV) in sub-Saharan Africa (SSA). The depression rate is higher in HIV-seropositive men who have sex with men (MSM) regardless of their sexual orientation, identity or romantic attraction. This is due to various types of stigma including HIV-related stigma, social stigma, self-stigma and mental health stigma. Opportunistic infections, unemployment, poverty and food insecurity also predispose HIV-seropositive MSM to depression. Moreover, depression in heterosexual and sexual minority groups challenges and additionally burdens SSA health care systems due to inadequate economic developments, lack of mental health professionals who specialise in the treatment of depression, few MSM-centred facilities, inadequate mental health infrastructure (hospitals and clinics) and complimentary resources. Although studies have highlighted links between mental health disorder, an HIV diagnosis and sexual minority groups, there is limited research that focusses on depression and its causal factors in MSM living with HIV in SSA. Hence, the relevance of conducting this scoping review.

Methods

A scoping review guided by Arksey and O’Malley’s framework, the enhancements and recommendations of Levac, Colquhoun and O’Brien, Daudt and associates and the 2015 Johanna Briggs Institute’s guidelines will be conducted. Systematic electronic searches of databases and search engines such as Google, Google Scholar, CINAHL (EBSCOhost), MEDLINE (Ovid), and PsycInfo (Ovid) will be conducted to attain published peer-reviewed articles of all study designs. Grey literature will be sourced from media and conference abstracts and reports, governmental reports and unpublished dissertations and theses. Additionally, websites of humanitarian organisations and other relevant departmental websites will also be searched. Literature published between 2010 and 2020 that meets the review’s inclusion criteria, research question and sub-question will be included in this review. All the retrieved literature will be exported to an Endnote X9.2 library after duplicates have been removed.

Discussion

We anticipate mapping relevant literature on depression and the causal factors in HIV-seropositive MSM living in SSA. Once analysed and summarised, the data will be useful in identifying literature gaps, informing systematic reviews and future research. The findings could also assist in depression and sexuality dialogues, and awareness campaigns that address mental health issues, stigma and discrimination among this key population living in SSA.
How beneficiaries see complex health interventions: a practice review of the Most Significant Change in ten countries
Authors: Tonkin Kendra , Silver Hilah , Pimentel Juan , Chomat Anne Marie , Sarmiento Ivan , Belaid Loubna , Cockcroft Anne , Andersson Neil
Published: February 2021

Background

The Most Significant Change is a story-based evaluation approach used in many international development programs. This practice review summarises practical experience with the approach in complex health interventions in ten countries, with the objective of making it more accessible in evaluation of other complex health interventions.

Results

Participatory research practitioners and trainees discussed five themes following brief presentations by each of the seven attendees who led the exercise: (i) sampling and recruitment; (ii) phrasing the questions to elicit stories; (iii) story collection strategies; (iv) quality assurance; and (v) analysis. Notes taken during the meeting provided the framework for this article.

Recruitment strategies in small studies included universal engagement and, in larger studies, a purposive, systematic or random sampling. Meeting attendees recommended careful phrasing and piloting of the question(s) as this affects the quality and focus of the stories generated. They stressed the importance of careful training and monitoring of fieldworkers collecting stories to ensure full stories are elicited and recorded. For recording, in most settings they preferred note taking with back-checking or self-writing of stories by story tellers, rather than audio-recording. Analysis can combine participatory selection of a small number of stories, deductive or inductive thematic analysis and discourse analysis. Meeting attendees noted that involvement in collection of the stories and their analysis and discussion had a positive impact for research team members.

Conclusions

Our review confirms the plasticity, feasibility and acceptability of the Most Significant Change technique across different sociopolitical, cultural and environmental contexts of complex interventions. Although the approach can surface unexpected impacts, it is not a 360-degree evaluation. Its strength lies in characterising the changes, where these happen, in the words of the beneficiaries. We hope this distillation of our practice makes the technique more readily available to health sector researchers.
Adoption of improved agricultural technology and its impact on household income: a propensity score matching estimation in eastern Ethiopia
Authors: Wordofa Muluken G. , Hassen Jemal Y. , Endris Getachew S. , Aweke Chanyalew S. , Moges Dereje K. , Rorisa Debbebe T.
Published: February 2021

Background

Adoption of improved agricultural technologies remains to be a promising strategy to achieve food security and poverty reduction in many developing countries. However, there are limited rigorous impact evaluations on the contributions of such technologies on household welfare. This paper investigates the impact of improved agricultural technology use on farm household income in eastern Ethiopia.

Methods

Primary data for the study was obtained from a random sample of 248 rural households, 119 of which are improved technology users and the rest are non-users. The research employed the Propensity Score Matching (PSM) procedure to establish the causal relationship between adoption of improved crop and livestock technologies and changes in farm income.

Results

Results from the econometric analysis show that households using improved agricultural technologies had, on average, 23,031.28 Birr (Birr is the official currency of Ethiopia. The exchange rate according to the National Bank of Ethiopia (NBE) was 1 USD = 27.6017 Birr on 04 October 2018.) higher annual farm income compared to those households not using such technologies. Our findings highlight the importance of promoting multiple and complementary agricultural technologies among rural smallholders.

Conclusions

We suggest that rural technology generation, dissemination and adoption interventions be strengthened. Moreover, the linkage among research, extension, universities and farmers needs to be enhanced through facilitating a multistakeholders innovation platforms.
A global, regional, and national survey on burden and Quality of Care Index (QCI) of hematologic malignancies; global burden of disease systematic analysis 1990–2017
Authors: Keykhaei Mohammad , Masinaei Masood , Mohammadi Esmaeil , Azadnajafabad Sina , Rezaei Negar , Saeedi Moghaddam Sahar , Rezaei Nazila , Nasserinejad Maryam , Abbasi-Kangevari Mohsen , Malekpour Mohammad-Reza , Ghamari Seyyed-Hadi , Haghshenas Rosa , Koliji Kamyar , Kompani Farzad , Farzadfar Farshad
Published: February 2021

Background

Hematologic malignancies (HMs) are a heterogeneous group of cancers that comprise diverse subgroups of neoplasms. So far, despite the major epidemiologic concerns about the quality of care, limited data are available for patients with HMs. Thus, we created a novel measure—Quality of Care Index (QCI)—to appraise the quality of care in different populations.

Methods

The Global Burden of Disease data from 1990 to 2017 applied in our study. We performed a principal component analysis on several secondary indices from the major primary indices, including incidence, prevalence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) to create the QCI, which provides an overall score of 0–100 of the quality of cancer care. We estimated the QCI for each age group on different scales and constructed the gender disparity ratio to evaluate the gender disparity of care in HMs.

Results

Globally, while the overall age-standardized incidence rate of HMs increased from 1990 to 2017, the age-standardized DALYs and death rates decreased during the same period. Across countries, in 2017, Iceland (100), New Zealand (100), Australia (99.9), and China (99.3) had the highest QCI scores for non-Hodgkin lymphoma, multiple myeloma, Hodgkin lymphoma, and leukemia. Conversely, Central African Republic (11.5 and 6.1), Eritrea (9.6), and Mongolia (5.4) had the lowest QCI scores for the mentioned malignancies respectively. Overall, the QCI score was positively associated with higher sociodemographic of nations, and was negatively associated with age advancing.

Conclusions

The QCI provides a robust metric to evaluate the quality of care that empowers policymakers on their responsibility to allocate the resources effectively. We found that there is an association between development status and QCI and gender equity, indicating that instant policy attention is demanded to improve health-care access.