bluuebunny/crossref_metadata_2025 huggingface dataset:
No detectable alloreactive transcriptional responses under standard sample preparation conditions during donor-multiplexed single-cell RNA sequencing of peripheral blood mononuclear cells
Authors: McGinnis Christopher S. , Siegel David A. , Xie Guorui , Hartoularos George , Stone Mars , Ye Chun J. , Gartner Zev J. , Roan Nadia R. , Lee Sulggi A.
Published: January 2021

Background

Single-cell RNA sequencing (scRNA-seq) provides high-dimensional measurements of transcript counts in individual cells. However, high assay costs and artifacts associated with analyzing samples across multiple sequencing runs limit the study of large numbers of samples. Sample multiplexing technologies such as MULTI-seq and antibody hashing using single-cell multiplexing kit (SCMK) reagents (BD Biosciences) use sample-specific sequence tags to enable individual samples to be sequenced in a pooled format, markedly lowering per-sample processing and sequencing costs while minimizing technical artifacts. Critically, however, pooling samples could introduce new artifacts, partially negating the benefits of sample multiplexing. In particular, no study to date has evaluated whether pooling peripheral blood mononuclear cells (PBMCs) from unrelated donors under standard scRNA-seq sample preparation conditions (e.g., 30 min co-incubation at 4 °C) results in significant changes in gene expression resulting from alloreactivity (i.e., response to non-self). The ability to demonstrate minimal to no alloreactivity is crucial to avoid confounded data analyses, particularly for cross-sectional studies evaluating changes in immunologic gene signatures.

Results

Here, we applied the 10x Genomics scRNA-seq platform to MULTI-seq and/or SCMK-labeled PBMCs from a single donor with and without pooling with PBMCs from unrelated donors for 30 min at 4 °C. We did not detect any alloreactivity signal between mixed and unmixed PBMCs across a variety of metrics, including alloreactivity marker gene expression in CD4+ T cells, cell type proportion shifts, and global gene expression profile comparisons using Gene Set Enrichment Analysis and Jensen-Shannon Divergence. These results were additionally mirrored in publicly-available scRNA-seq data generated using a similar experimental design. Moreover, we identified confounding gene expression signatures linked to PBMC preparation method (e.g., Trima apheresis), as well as SCMK sample classification biases against activated CD4+ T cells which were recapitulated in two other SCMK-incorporating scRNA-seq datasets.

Conclusions

We demonstrate that (i) mixing PBMCs from unrelated donors under standard scRNA-seq sample preparation conditions (e.g., 30 min co-incubation at 4 °C) does not cause an allogeneic response, and (ii) that Trima apheresis and PBMC sample multiplexing using SCMK reagents can introduce undesirable technical artifacts into scRNA-seq data. Collectively, these observations establish important benchmarks for future cross-sectional immunological scRNA-seq experiments.
Translational landscape and protein biogenesis demands of the early secretory pathway in Komagataella phaffii
Authors: Alva Troy R. , Riera Melanie , Chartron Justin W.
Published: January 2021

Background

Eukaryotes use distinct networks of biogenesis factors to synthesize, fold, monitor, traffic, and secrete proteins. During heterologous expression, saturation of any of these networks may bottleneck titer and yield. To understand the flux through various routes into the early secretory pathway, we quantified the global and membrane-associated translatomes of Komagataella phaffii.

Results

By coupling Ribo-seq with long-read mRNA sequencing, we generated a new annotation of protein-encoding genes. By using Ribo-seq with subcellular fractionation, we quantified demands on co- and posttranslational translocation pathways. During exponential growth in rich media, protein components of the cell-wall represent the greatest number of nascent chains entering the ER. Transcripts encoding the transmembrane protein PMA1 sequester more ribosomes at the ER membrane than any others. Comparison to Saccharomyces cerevisiae reveals conservation in the resources allocated by gene ontology, but variation in the diversity of gene products entering the secretory pathway.

Conclusion

A subset of host proteins, particularly cell-wall components, impose the greatest biosynthetic demands in the early secretory pathway. These proteins are potential targets in strain engineering aimed at alleviating bottlenecks during heterologous protein production.
The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment
Authors: Emami Nejad Asieh , Najafgholian Simin , Rostami Alireza , Sistani Alireza , Shojaeifar Samaneh , Esparvarinha Mojgan , Nedaeinia Reza , Haghjooy Javanmard Shaghayegh , Taherian Marjan , Ahmadlou Mojtaba , Salehi Rasoul , Sadeghi Bahman , Manian Mostafa
Published: January 2021

Hypoxia is a common feature of solid tumors, and develops because of the rapid growth of the tumor that outstrips the oxygen supply, and impaired blood flow due to the formation of abnormal blood vessels supplying the tumor. It has been reported that tumor hypoxia can: activate angiogenesis, thereby enhancing invasiveness and risk of metastasis; increase survival of tumor, as well as suppress anti-tumor immunity and hamper the therapeutic response. Hypoxia mediates these effects by several potential mechanisms: altering gene expression, the activation of oncogenes, inactivation of suppressor genes, reducing genomic stability and clonal selection. We have reviewed the effects of hypoxia on tumor biology and the possible strategiesto manage the hypoxic tumor microenvironment (TME), highlighting the potential use of cancer stem cells in tumor treatment.
TRAIL promotes hepatocellular carcinoma apoptosis and inhibits proliferation and migration via interacting with IER3
Authors: Liu Shihai , Qiu Jing , He Guifang , He Weitai , Liu Changchang , Cai Duo , Pan Huazheng
Published: January 2021

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce substantial cytotoxicity in tumor cells but rarely exert cytotoxic activity on non-transformed cells. In the present study, we therefore evaluated interactions between TRAIL and IER3 via co-immunoprecipitation and immunofluorescence analyses, leading us to determine that these two proteins were able to drive the apoptotic death of hepatocellular carcinoma (HCC) cells and to disrupt their proliferative and migratory abilities both in vitro and in vivo. From a mechanistic perspective, we determined that TRAIL and IER3 were capable of inhibiting Wnt/β-catenin signaling. Together, these results indicate that TRAIL can control the pathogenesis of HCC at least in part via interacting with IER3 to inhibit Wnt/β-catenin signaling, thus indicating that this TRAIL/IER3/β-catenin axis may be a viable therapeutic target in HCC patients.
Conditional survival after surgical resection of primary retroperitoneal tumors: a population-based study
Authors: Zhao Shutao , Zhao Yixuan , Liu Shuang , Zhang Chao , Wang Xudong
Published: January 2021

Background

The purpose of this study was to assess conditional survival (CS) after resection of primary retroperitoneal tumors (RPTs).

Methods

The data of 1594 patients with primary RPTs who underwent surgery between 2004 and 2016 were retrieved from the Surveillance Epidemiology and End Results (SEER) database. Multivariate Cox analysis was used to identify prognostic factors affecting overall survival (OS) and cancer-specific survival (CSS). CS was used to calculate the probability of survival for an additional 3 years after the patient had survived x years, according to the formulas: COS3 = OS (x + 3) /OS (x) and CCSS3 = CSS (x + 3)/CSS (x).

Results

The 1-, 3-, and 5-year OS rates of all patients were 89.8, 71.8, and 60.8%, while the 1-, 3-, and 5-year CSS rates were 91.9, 77.1, and 67.8%, respectively. Age, sex, FNCLCC grade, size, multifocality, histology, and chemotherapy were independent prognostic factors for OS and CSS. Among patients who survived for 1, 3, and 5 years, the COS3 rates were 72.9, 77.9, and 79.3%, and the CCSS3 rates were 78.1, 82.7, and 85.8%, respectively. Patients with poor clinicopathological characteristics achieved greater improvements in COS3 and CCSS3 rates, and the survival gaps between OS and COS3, as well as CSS and CCSS3 were more obvious.

Conclusion

Postoperative CS of RPTs was dynamic and increased over time. CS increased more significantly in patients with poor clinicopathological characteristics.
Choosing interventions to eliminate forest malaria: preliminary results of two operational research studies inside Cambodian forests
Authors: Kunkel Amber , Nguon Chea , Iv Sophea , Chhim Srean , Peov Dom , Kong Phanith , Kim Saorin , Im Sarun , Debackere Mark , Khim Nimol , Popovici Jean , Srun Sreynet , Vantaux Amélie , Guintran Jean-Olivier , Witkowski Benoit , Piola Patrice
Published: January 2021

Background

Rapid elimination of Plasmodium falciparum malaria in Cambodia is a goal with both national and international significance. Transmission of malaria in Cambodia is limited to forest environments, and the main population at risk consists of forest-goers who rely on forest products for income or sustenance. The ideal interventions to eliminate malaria from this population are unknown.

Methods

In two forested regions of Cambodia, forest-goers were trained to become forest malaria workers (FMWs). In one region, FMWs performed mass screening and treatment, focal screening and treatment, and passive case detection inside the forest. In the other region, FMWs played an observational role for the first year, to inform the choice of intervention for the second year. In both forests, FMWs collected blood samples and questionnaire data from all forest-goers they encountered. Mosquito collections were performed in each forest.

Results

Malaria prevalence by PCR was high in the forest, with 2.3–5.0% positive for P. falciparum and 14.6–25.0% positive for Plasmodium vivax among forest-goers in each study site. In vectors, malaria prevalence ranged from 2.1% to 9.6%, but no P. falciparum was observed. Results showed poor performance of mass screening and treatment, with sensitivity of rapid diagnostic tests equal to 9.1% (95% CI 1.1%, 29.2%) for P. falciparum and 4.4% (95% CI 1.6%, 9.2%) for P. vivax. Malaria infections were observed in all demographics and throughout the studied forests, with no clear risk factors emerging.

Conclusions

Malaria prevalence remains high among Cambodian forest-goers, but performance of rapid diagnostic tests is poor. More adapted strategies to this population, such as intermittent preventive treatment of forest goers, should be considered.
Overuse or underuse? Use of healthcare services among irregular migrants in a north-eastern Spanish region
Authors: Gimeno-Feliu Luis Andrés , Pastor-Sanz Marta , Poblador-Plou Beatriz , Calderón-Larrañaga Amaia , Díaz Esperanza , Prados-Torres Alexandra
Published: January 2021

Background

There is little verified information on global healthcare utilization by irregular migrants. Understanding how immigrants use healthcare services based on their needs is crucial to establish effective health policy. We compared healthcare utilization between irregular migrants, documented migrants, and Spanish nationals in a Spanish autonomous community.

Methods

This retrospective, observational study included the total adult population of Aragon, Spain: 930,131 Spanish nationals; 123,432 documented migrants; and 17,152 irregular migrants. Healthcare utilization data were compared between irregular migrants, documented migrants and Spanish nationals for the year 2011. Multivariable standard or zero-inflated negative binomial regression models were generated, adjusting for age, sex, length of stay, and morbidity burden.

Results

The average annual use of healthcare services was lower for irregular migrants than for documented migrants and Spanish nationals at all levels of care analyzed: primary care (0.5 vs 4 vs 6.7 visits); specialized care (0.2 vs 1.8 vs 2.9 visits); planned hospital admissions (0.3 vs 2 vs 4.23 per 100 individuals), unplanned hospital admissions (0.5 vs 3.5 vs 5.2 per 100 individuals), and emergency room visits (0.4 vs 2.8 vs 2.8 per 10 individuals). The average annual prescription drug expenditure was also lower for irregular migrants (€9) than for documented migrants (€77) and Spanish nationals (€367). These differences were only partially attenuated after adjusting for age, sex, and morbidity burden.

Conclusions

Under conditions of equal access, healthcare utilization is much lower among irregular migrants than Spanish nationals (and lower than that of documented migrants), regardless of country of origin or length of stay in Spain.
Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance
Authors: Chang Bo , Song Chenglin , Gao Haining , Ma Tie , Li Tao , Ma Qianhe , Yao Tingting , Wang Meng , Li Jing , Yi Xuejie , Tang Donghui , Cao Shicheng
Published: January 2021

Background

Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis.

Methods

Four-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively.

Results

Compared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT.

Conclusion

During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.
Caring Behaviors Inventory-24: translation, cross-cultural adaptation and psychometric testing for use in a Swedish context
Authors: Klarare Anna , Söderlund Mona , Wikman Anna , McGreevy Jenny , Mattsson Elisabet , Rosenblad Andreas
Published: January 2021

Background

Patients’ health and wellbeing are promoted when nurses successfully conceptualize caring in clinical practice. Measuring caring behaviors can advance knowledge about caring and has potential to improve caring practices and the outcomes of care. The Caring Behaviors Inventory-24 (CBI-24) is an empirical instrument for measuring caring, developed to determine perceptions of caring among patients and nurses. Since the instrument was not available in Swedish, the aim of this study was therefore to translate into Swedish and cross-culturally adapt CBI-24 for a Swedish healthcare context, and to psychometrically analyze the Swedish version of CBI-24.

Methods

The study used a traditional forward and back translation process in six stages: (1) two simultaneous translations by bilingual experts; (2) expert review committee synthesis; (3) blind back translation; (4) expert review committee deliberations; (5) pre-testing with cognitive interviews, and (6) psychometric evaluations.

Results

The translation process was systematically conducted and entailed discussions regarding semantic, idiomatic, experiential and conceptual equivalence. The cognitive interviews generated thoughts and reflections, which resulted in adjusting three items of the CBI-24 SWE. For psychometric analyses, 234 persons answered the questionnaire. Results indicated acceptable overall model fit in the χ2-value for the confirmatory factor analysis, while for the heuristic goodness-of-fit indices, the comparative fit index (CFI) and the standardized mean square residual (SMSR) indicated good model fits, and the root mean square error approximation (RMSEA) indicated an acceptable fit.

Conclusions

CBI-24 SWE has been shown to be a psychometrically acceptable instrument for use in Swedish research contexts. Further studies regarding the clinical usefulness of the instrument may be in order. In particular, CBI-24 SWE should be evaluated among nurses in rural areas.
What makes a ‘successful’ collaborative research project between public health practitioners and academics? A mixed-methods review of funding applications submitted to a local intervention evaluation scheme
Authors: van der Graaf Peter , Blank Lindsay , Holding Eleanor , Goyder Elizabeth
Published: January 2021

Background

The national Public Health Practice Evaluation Scheme (PHPES) is a response-mode funded evaluation programme operated by the National Institute for Health Research School for Public Health Research (NIHR SPHR). The scheme enables public health professionals to work in partnership with SPHR researchers to conduct rigorous evaluations of their interventions. Our evaluation reviewed the learning from the first five years of PHPES (2013–2017) and how this was used to implement a revised scheme within the School.

Methods

We conducted a rapid review of applications and reports from 81 PHPES projects and sampled eight projects (including unfunded) to interview one researcher and one practitioner involved in each sampled project (n = 16) in order to identify factors that influence success of applications and effective delivery and dissemination of evaluations. Findings from the review and interviews were tested in an online survey with practitioners (applicants), researchers (principal investigators [PIs]) and PHPES panel members (n = 19) to explore the relative importance of these factors. Findings from the survey were synthesised and discussed for implications at a national workshop with wider stakeholders, including public members (n = 20).

Results

Strengths: PHPES provides much needed resources for evaluation which often are not available locally, and produces useful evidence to understand where a programme is not delivering, which can be used to formatively develop interventions. Weaknesses: Objectives of PHPES were too narrowly focused on (cost-)effectiveness of interventions, while practitioners also valued implementation studies and process evaluations. Opportunities: PHPES provided opportunities for novel/promising but less developed ideas. More funded time to develop a protocol and ensure feasibility of the intervention prior to application could increase intervention delivery success rates. Threats: There can be tensions between researchers and practitioners, for example, on the need to show the 'success’ of the intervention, on the use of existing research evidence, and the importance of generalisability of findings and of generating peer-reviewed publications.

Conclusions

The success of collaborative research projects between public health practitioners (PHP) and researchers can be improved by funders being mindful of tensions related to (1) the scope of collaborations, (2) local versus national impact, and (3) increasing inequalities in access to funding. Our study and comparisons with related funding schemes demonstrate how these tensions can be successfully resolved.
Challenges in the abortion supply chain: a call to action for evaluation research
Authors: Samandari Ghazaleh , Kapp Nathalie , Hamon Christopher , Campbell Allison
Published: January 2021

Background

Reducing the burden of unsafe abortion rests considerably on women’s ability to access appropriate and timely treatment or services. A critical component of that care relies on a functional supply chain to ensure availability of abortion drugs and supplies within the health system. Disruptions in the supply of medical abortion drugs delay provision of abortion services and can increase the risks to a woman’s health. We examine the ways in which supply chain management (SCM) affects women’s ability to access safe and timely abortion to meet their reproductive health needs and highlight the gap in evaluation research on which SCM interventions best improve access to safe abortion care.

SCM comprises a critical component of efficient and sustainable abortion service provision and is a requisite for expansion of services. Furthermore, governments are responsible for safeguarding links in the abortion supply chain, from registration to distribution of abortion drugs and supplies. Strategic public–private partnerships and use of innovative local or community-based distribution mechanisms can strengthen supply chain systems. Finally, alternatives to the pull-based models of distribution could alleviate bottlenecks in the final steps of abortion supply chains. Programs aimed at increasing access to safe and comprehensive abortion care must include SCM as a foundational component of service provision. Without access to a sustainable and affordable supply of abortion drugs and equipment, any attempt at providing abortion services will be critically limited. More implementation research is needed to identify the most effective interventions for improving SCM.
Delivery strategies for optimizing uptake of contraceptives among adolescents aged 15–19 years in Nsanje District, Malawi
Authors: Makwinja Andrew Kondaine , Maida Zione Mchikaya , Nyondo-Mipando Alinane Linda
Published: January 2021

Background

Despite documented benefits of contraceptives, uptake among young people aged 20–24 years is high compared to adolescents aged 15–19 years in Malawi. As the world’s population of 15–19-year-olds continues to grow the need to meet the increasing demand for contraceptive services and information that address adolescent-specific needs cannot be underestimated. To inform Sexual and Reproductive health services for the youth, we explored strategies for optimizing uptake of contraceptives among this age group.

Methods

An exploratory qualitative cross-sectional study was conducted at Nsanje District Hospital and Nyamadzere Community Day Secondary School guided by Social-Ecological Framework to understand strategies that may optimize the uptake of contraceptives among adolescents aged 15–19. Nsanje district was purposively selected based on the reason that it is the second district in Malawi with the highest rate of adolescent childbearing of girls aged 15–19 years. We conducted a Focus Group Discussion (FGD) with 9 traditional leaders, 11 Key Informant Interviews (KIIs) with health workers, 20 In-depth Interviews (IDIs) with 12 adolescents, 4 teachers, and 4 parents. All data were digitally recorded, transcribed verbatim into English. The data was analyzed and managed using deductive thematic analysis guided by Social-Ecological Framework.

Results

Adolescents suggested accessing contraceptives from local drug stores, pharmacies and hospitals at a health system level and through Youth Centres, clubs, and corners at a Community level. There is a need to ensure a continuous supply of various kinds of contraceptives and the presence of youth-friendly health care workers in the specified areas.

Conclusion

There is no one way of delivering contraceptives to adolescents. Multiple avenues existent at the health facility and community could be leveraged to optimize delivery and uptake of contraceptives in a manner that is not intimidating to an adolescent while involving key stakeholders.
Apparent diffusion coefficient for the prediction of tumor response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer
Authors: Zhao Mengjing , Zhao Lihao , Yang Han , Duan Yuxia , Li Gang
Published: January 2021

Background

Patients with locally advanced rectal cancer generally have different response rates to preoperative neoadjuvant chemo-radiotherapy. This study investigated the value of the apparent diffusion coefficient (ADC) as a predictor to forecast the response to neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer.

Methods

Ninety-one locally advanced rectal cancer patients who underwent neoadjuvant chemo-radiotherapy between 2015 and 2018 were enrolled. Diffusion-weighted magnetic resonance imaging was performed before treatment and within 4 weeks after the completion of neoadjuvant chemo-radiotherapy. Mean ADC values of regions of interest were evaluated by two radiologists. The tumor response was evaluated according to RESCIST 1.1. The cut-off value for the mean ADC and increasing percentage (ΔADC%) after neoadjuvant chemo-radiotherapy was calculated using the receiver operating characteristic curve. The response rate of pre-ADC and ΔADC% above/below the cut-off values was determined using the chi-square test, respectively. Primary tumor progression-free survival (PFS) was analyzed using the Kaplan–Meier method, based on the pre-ADC and ΔADC% cut-off values.

Results

The cut-off value of mean pre-ADC and ΔADC% was 0.94 × 10–3 mm2/s (80.36% sensitivity, 74.29% specificity) and 26.0% (73.21% sensitivity, 77.14% specificity), respectively. Lower mean pre-ADC values were related to a better response rate (83.3% vs 29.7%, P < 0.001) and PFS (26.12 vs 17.70 months, P = 0.004). ΔADC% above the cut-off value was also related to a better response rate (83.7% vs 35.7%, P < 0.001) and PFS (26.93 vs 15.65 months, P = 0.034).

Conclusions

The mean ADC pre-treatment value and ΔADC% were potential predictors for the tumor response in locally advanced rectal cancer patients treated with neoadjuvant chemo-radiotherapy.
Case series and finite element analysis of PFNA combined with cerclage wire for treatment of subtrochanteric fracture of femur
Authors: Huang Xiaowei , Zhang Fangxue , Zhang Yong
Published: January 2021

Objective

To retrospectively analyze the clinical efficacy of PFNA combined with a cerclage wire in the treatment of 52 patients with unstable subtrochanteric fracture of the femur and to analyze the biomechanical effect of ligature on a fracture model.

Methods

In this study, 52 patients with unstable subtrochanteric fractures were treated in our orthopedic trauma center from June 2013 to July 2018. The Seinsheimer type IV fracture model was established using the patient’s CT data, and the joint surface of the distal femoral condyle and the external condyle were restrained. The femoral head was used as the loading point, and a force of 500 N was applied vertically along the long axis of the femoral shaft.

Results

All 52 patients were followed up for 12 to 37 months, with an average of 18.07 ± 4.38 months. According to the Sanders hip function score, 28 cases were excellent (55–60 points), 22 cases were good (45–54 points), and 2 cases were poor (35–44 points), with an excellent and good rate of 96.15%. Postoperative deep vein thrombosis occurred in 3 cases, and fracture nonunion occurred in 1 case. No infection, loose fracture of internal fixation or hip varus deformity occurred. The finite element analysis indicated that the displacement of the whole model decreased slightly and the relative sliding of the fracture block decreased, but the maximum stress of the femur increased after the addition of the cerclage wire.

Conclusion

The treatment of unstable subtrochanteric fracture of the femur with PFNA combined with cerclage wire has the advantages of simple operation, satisfactory reduction of fracture, stable fixation, and good recovery of limb function. The finite element analysis suggested that the biomechanical strength fixation was enhanced after the addition of cerclage wire. However, the local stress concentration of the tie may increase the risk of failure.
Pancreatic involvement in patients with inborn errors of metabolism
Authors: Hwang Woo Jin , Lim Han Hyuk , Kim Yoo-Mi , Chang Mea Young , Kil Hong Ryang , Kim Jae Young , Song Wung Joo , Levy Harvey L. , Kim Sook-Za
Published: January 2021

Background

Repeated inflammation of the pancreas can cause pancreatitis or diabetes. It is well recognized that the organic acidemias may be complicated by pancreatitis but less recognized are other metabolic disorders in which pancreatitis can occur. This study shows that long-term follow-up of patients with various metabolic disorders in Korea revealed several with episodes of isolated pancreatitis or diabetes concomitantly with pancreatitis.

Results and discussion

In this study, two patients with methylmalonic aciduria (MMA), two with propionic acidemia (PPA), one with fatty acid oxidation disorder (FAOD), and one with hyperornithinemia, gyrate atrophy, and juvenile onset diabetes mellitus (DM) were clinically followed for up to 10 – 21 years. Two Korean siblings with MMA showed recurrent pancreatitis from the age of 15 and 19, respectively. The frequency of admission due to pancreatitis was up to 11 times. One patient with MMA developed diabetes mellitus at the age of 20. The other patient with MMA developed recurrent pancreatitis at 4 years and diabetes at 8 years of age. One of the patients with PPA presented with diabetic ketoacidosis. The other PPA patient died of cardiac arrest at age 10. The patient with FAOD presented with pancreatitis at 10 years and died at the age of 15 years due to cardiac arrest. A 35-year-old woman with hyperornithinemia/gyrate atrophy was diagnosed with juvenile onset diabetes at the age of 7 years. No pancreatitis occurred during the follow-up period.

Conclusions

We conclude that various metabolic disorders can trigger acute or chronic pancreatitis. Proper and prompt multidisciplinary management of metabolic derangement is crucial for preventing pancreatic damage. Further clinical and investigational studies are required to elucidate the pathogenesis of pancreatitis and diabetes mellitus in patients with inborn errors in metabolism.
An efficient computational method for predicting drug-target interactions using weighted extreme learning machine and speed up robot features
Authors: An Ji-Yong , Meng Fan-Rong , Yan Zi-Ji
Published: January 2021

Background

Prediction of novel Drug–Target interactions (DTIs) plays an important role in discovering new drug candidates and finding new proteins to target. In consideration of the time-consuming and expensive of experimental methods. Therefore, it is a challenging task that how to develop efficient computational approaches for the accurate predicting potential associations between drug and target.

Results

In the paper, we proposed a novel computational method called WELM-SURF based on drug fingerprints and protein evolutionary information for identifying DTIs. More specifically, for exploiting protein sequence feature, Position Specific Scoring Matrix (PSSM) is applied to capturing protein evolutionary information and Speed up robot features (SURF) is employed to extract sequence key feature from PSSM. For drug fingerprints, the chemical structure of molecular substructure fingerprints was used to represent drug as feature vector. Take account of the advantage that the Weighted Extreme Learning Machine (WELM) has short training time, good generalization ability, and most importantly ability to efficiently execute classification by optimizing the loss function of weight matrix. Therefore, the WELM classifier is used to carry out classification based on extracted features for predicting DTIs. The performance of the WELM-SURF model was evaluated by experimental validations on enzyme, ion channel, GPCRs and nuclear receptor datasets by using fivefold cross-validation test. The WELM-SURF obtained average accuracies of 93.54, 90.58, 85.43 and 77.45% on enzyme, ion channels, GPCRs and nuclear receptor dataset respectively. We also compared our performance with the Extreme Learning Machine (ELM), the state-of-the-art Support Vector Machine (SVM) on enzyme and ion channels dataset and other exiting methods on four datasets. By comparing with experimental results, the performance of WELM-SURF is significantly better than that of ELM, SVM and other previous methods in the domain.

Conclusion

The results demonstrated that the proposed WELM-SURF model is competent for predicting DTIs with high accuracy and robustness. It is anticipated that the WELM-SURF method is a useful computational tool to facilitate widely bioinformatics studies related to DTIs prediction.
Association analysis of repetitive elements and R-loop formation across species
Authors: Zeng Chao , Onoguchi Masahiro , Hamada Michiaki
Published: January 2021

Background

Although recent studies have revealed the genome-wide distribution of R-loops, our understanding of R-loop formation is still limited. Genomes are known to have a large number of repetitive elements. Emerging evidence suggests that these sequences may play an important regulatory role. However, few studies have investigated the effect of repetitive elements on R-loop formation.

Results

We found different repetitive elements related to R-loop formation in various species. By controlling length and genomic distributions, we observed that satellite, long interspersed nuclear elements (LINEs), and DNA transposons were each specifically enriched for R-loops in humans, fruit flies, and Arabidopsis thaliana, respectively. R-loops also tended to arise in regions of low-complexity or simple repeats across species. We also found that the repetitive elements associated with R-loop formation differ according to developmental stage. For instance, LINEs and long terminal repeat retrotransposons (LTRs) are more likely to contain R-loops in embryos (fruit fly) and then turn out to be low-complexity and simple repeats in post-developmental S2 cells.

Conclusions

Our results indicate that repetitive elements may have species-specific or development-specific regulatory effects on R-loop formation. This work advances our understanding of repetitive elements and R-loop biology.
Impact of Polyvalent Mechanical Bacterial Lysate on lymphocyte number and activity in asthmatic children: a randomized controlled trial
Authors: Bartkowiak-Emeryk Małgorzata , Emeryk Andrzej , Roliński Jacek , Wawryk-Gawda Ewelina , Markut-Miotła Ewa
Published: January 2021

Background

Polyvalent Mechanical Bacterial Lysate (PMBL®) contains antigens of bacteria responsible for respiratory infections. PMBL® has been proven to reduce the number of respiratory infections, and in its use, immunological benefits have been seen in allergic patients. PMBL® activates both innate and specific immune responses. The lysate induces dendritic cells, T and B lymphocytes and IgA secretion, as well as the production of antibodies directed against administered bacterial antigens. Moreover, it increases the response against other bacteria and viruses. The immunologic mechanism of lysate’s action is not yet clearly determined. The objective of this study was to assess the effect of PMBL® on T cells in children with allergic asthma.

Methods

This study was a part of the EOLIA study. Herein, 49 children with allergic asthma and house dust mites allergy were included: 21 in PMBL® and 28 in the Placebo group, both, drug and placebo were administered sublingually. The tests were done at baseline and 12 weeks after the last tablet intake. The lymphocytes CD45+, lymphocytes T CD3+, CD3+CD25+, CD3+CD69+, Th CD3+CD4+, CD4+CD25+, CD4+CD25+ high, CD4+CD69+, Treg CD4+CD25+FOXP3, Tc CD3+CD8+, CD8+CD25+, CD8+CD69+, NK-like T CD3+CD16+CD56+ and NK cells CD3−CD16+CD56+ were described.

Results

At baseline, no significant differences between groups relative to blood count cells were observed, except for eosinophils. After 12 weeks, we observed an increase of T lymphocytes count. In addition, CD4+CD25+FOXP3+, CD8+ and CD3−CD16+CD56+ and (insignificantly) Th count increased. However, CD69+ and CD25+ subset of CD3+ significantly decreased.

Conclusions

The EOLIA study demonstrated that PMBL® administration 10 days per month for 3 months changed the panel of T lymphocytes.

Trial registration Clinical Trial Registration: This study was a part of the EOLIA (Efficacy Of mechanical bacterial Lysate In Allergic children), a clinical study NCT02541331. Frederic Durmont, MD Lallemand Pharma International AG. Date of registration 09/08/2013. URL of trial registry record: https://clinicaltrials.gov/ct2/show/study/NCT02541331.
Sero- and apx-typing of German Actinobacillus pleuropneumoniae field isolates from 2010 to 2019 reveals a predominance of serovar 2 with regular apx-profile
Authors: Schuwerk Lukas , Hoeltig Doris , Waldmann Karl-Heinz , Valentin-Weigand Peter , Rohde Judith
Published: January 2021

Serotyping is the most common method to characterize field isolates of Actinobacillus (A.) pleuropneumoniae, the etiological agent of porcine pleuropneumonia. Based on serology, many farms seem to be infected and antibodies against a wide variety of serovars are detectable, but, so far it is unknown to what degree respective serovars contribute to outbreaks of clinical manifest disease. In this study, 213 German A. pleuropneumoniae field isolates retrieved for diagnostic purposes from outbreaks of porcine pleuropneumonia between 2010 and 2019 were genetically serotyped and analyzed regarding their apx-toxin gene profile using molecular methods. Serotyping revealed a prominent role of serovar 2 in clinical cases (64% of all isolates) and an increase in the detection of this serovar since 2010 in German isolates. Serovar 9/11 followed as the second most frequent serovar with about 15% of the isolates. Furthermore, very recently described serovars 16 (n = 2) and 18 (n = 8) were detected. Most isolates (93.4%) showed apx-profiles typical for the respective serovar. However, this does not hold true for isolates of serovar 18, as 75% (n = 6) of all isolates of this serovar deviated uniformly from the “typical” apx-gene profile of the reference strain 7311555. Notably, isolates from systemic lesions such as joints or meninges did not harbor the complete apxICABD operon which is considered typical for highly virulent strains. Furthermore, the extremely low occurrence (n = 1) of NAD independent (biovar II) isolates in German A. pleuropneumoniae was evident in our collection of clinical isolates.
Retraction Note: Proofs to one inequality conjecture for the non-integer part of a nonlinear differential form
Authors: Chen Mei
Published: January 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13660-021-02555-5
WISE: a computer system performance index scoring framework
Authors: Luciano Lorenzo , Kiss Imre , Beardshear Peter William , Kadosh Esther , Hamza A. Ben
Published: January 2021

The performance levels of a computing machine running a given workload configuration are crucial for both users and providers of computing resources. Knowing how well a computing machine is running with a given workload configuration is critical to making proper computing resource allocation decisions. In this paper, we introduce a novel framework for deriving computing machine and computing resource performance indicators for a given workload configuration. We propose a workload/machine index score (WISE) framework for computing a fitness score for a workload/machine combination. The WISE score indicates how well a computing machine is running with a specific workload configuration by addressing the issue of whether resources are being stressed or sitting idle wasting precious resources. In addition to encompassing any number of computing resources, the WISE score is determined by considering how far from target levels the machine resources are operating at without maxing out. Experimental results demonstrate the efficacy of the proposed WISE framework on two distinct workload configurations.
Multiple clinical risks for cannabis users during the COVID-19 pandemic
Authors: Borgonhi Ellen Mello , Volpatto Vanessa Loss , Ornell Felipe , Rabelo-da-Ponte Francisco Diego , Kessler Felix Henrique Paim
Published: January 2021

The pandemic caused by Sars-CoV-2 (COVID-19) has been a great concern for public and mental health systems worldwide. The identification of risk groups is essential for the establishment of preventive and therapeutic strategies, as for substance users. During COVID-19 pandemic, there was an increase in the use of psychoactive substances during the lockdown, including cannabis. This commentary reviews relevant findings and discusses scientific evidence on the risks of worse clinical and psychiatric complications due to coronavirus disease COVID-19 in subjects who use cannabis. Although they are not included as a risk group in the health recommendations for that disease, they may have a more vulnerable respiratory system to viral diseases. There are certain similarities between the harmful cardiovascular and respiratory effects of cannabis use and those of smoking. Due to the different modes of smoking, cannabis chemicals are retained in the body for longe and may also contain other toxic substances such as tar, a substance found in tobacco and which has been associated with the development of lung cancer, bronchitis and pulmonary emphysema. Therefore, we discuss if individuals who use cannabis regularly might be more vulnerable to COVID-19 infection. This population deserves more clinical attention worldwide and this manuscript can help clinicians become more aware of cannabis risks during pandemics and develop specific intervention strategies.
COVID-19, anorexia nervosa and obese patients with an eating disorder - some considerations for practitioners and researchers
Authors: Simeunovic Ostojic Mladena , Maas Joyce , Bodde Nynke M. G.
Published: January 2021

Since COVID-19 is a global health emergency, there is an urgent need to share experiences on decision-making with regard to safety recommendations and for hypotheses that can inform a more focused prevention and treatment. Moreover, combining research into eating disorders and obesity with research into COVID-19 may provide a unique opportunity to shed light on the susceptibility to COVID-19.
Semi-analytical solutions of seismo-electromagnetic signals arising from the motional induction in 3-D multi-layered media: part I—theoretical formulations
Authors: Sun Yao-Chong , Ren Hengxin , Yamazaki Ken’ichi , Zeng Ling , Huang Qinghua , Chen Xiaofei
Published: January 2021

Taking into account the motional induction effect, in which the Earth crust that has finite electrical conductivity vibrates in the ambient geomagnetic field resulting in motionally induced electric current, we derive semi-analytical solutions of seismo-electromagnetic signals generated by an earthquake source in 3-D multi-layered media, which consists of an air half-space and multiple solid layers. First, both the elastic and electromagnetic (EM) wave-fields involved in the governing equations, which have the form of Maxwell’s equations coupled with elastodynamic equations, are expanded by a set of vector basis functions in cylindrical coordinate system. Then, we reorganize the transformed governing equations expressed by expansion coefficients and obtain corresponding first-order ordinary differential equations for the wave-fields in air and solid media. The expansion of the motionally induced electric current and the reorganization of Maxwell’s equations are the most important part, and also the most complicated and tedious part of this work. Thereafter, we solve the first-order ordinary differential equations through the Luco–Apsel–Chen generalized reflection and transmission method gaining solutions of the expansion coefficients. Finally, we obtain the frequency–space-domain semi-analytical solutions written as integrations of corresponding expansion coefficients over wavenumber domain, which can be numerically calculated by the discrete wavenumber method. The time-domain solutions can be achieved by further applying the discrete inverse Fourier transform. To have a numerical stability at any high frequency, we adopt the analytical regularization approach in the derivation process by introducing two artificial interfaces with infinitely small distance from the source. On the basis of the semi-analytical solutions, we can tell that only EM fields of TM mode (in which magnetic fields are transversely polarized) will be induced by SH waves, whereas EM fields of both TE mode (in which magnetic fields are transversely polarized) and TM mode will be induced by P and SV waves. The derived semi-analytical solutions can be used to calculate seismo-electromagnetic signals either below or above the free surface.
Alignment determination of the Hayabusa2 laser altimeter (LIDAR)
Authors: Noda Hirotomo , Senshu Hiroki , Matsumoto Koji , Namiki Noriyuki , Mizuno Takahide , Sugita Seiji , Abe Shinsuke , Araki Hiroshi , Asari Kazuyoshi , Cho Yuichiro , Fujii Atsushi , Hayakawa Masahiko , Higuchi Arika , Hirata Naoyuki , Hirata Naru , Honda Chikatoshi , Honda Rie , Ishihara Yoshiaki , Kameda Shingo , Kikuchi Shota , Kouyama Toru , Matsuoka Moe , Mimasu Yuya , Morota Tomokatsu , Nakazawa Satoru , Ogawa Kazunori , Ogawa Naoko , Ono Go , Oshigami Shoko , Saiki Takanao , Sakatani Naoya , Sasaki Sho , Sawada Hirotaka , Shizugami Makoto , Suzuki Hidehiko , Takahashi Tadateru , Takei Yuto , Tanaka Satoshi , Tatsumi Eri , Terui Fuyuto , Tsuda Yuichi , Tsuruta Seiitsu , Watanabe Sei-ichiro , Yamada Manabu , Yamada Ryuhei , Yamaguchi Tomohiro , Yamamoto Keiko , Yokota Yasuhiro , Yoshida Fumi , Yoshikawa Kent , Yoshikawa Makoto , Yoshioka Kazuo
Published: January 2021

In this study, we determined the alignment of the laser altimeter aboard Hayabusa2 with respect to the spacecraft using in-flight data. Since the laser altimeter data were used to estimate the trajectory of the Hayabusa2 spacecraft, the pointing direction of the altimeter needed to be accurately determined. The boresight direction of the receiving telescope was estimated by comparing elevations of the laser altimeter data and camera images, and was confirmed by identifying prominent terrains of other datasets. The estimated boresight direction obtained by the laser link experiment in the winter of 2015, during the Earth’s gravity assist operation period, differed from the direction estimated in this study, which fell on another part of the candidate direction; this was not selected in a previous study. Assuming that the uncertainty of alignment determination of the laser altimeter boresight was 4.6 pixels in the camera image, the trajectory error of the spacecraft in the cross- and/or along-track directions was determined to be 0.4, 2.1, or 8.6 m for altitudes of 1, 5, or 20 km, respectively.