bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment of a 5-gene risk model related to regulatory T cells for predicting gastric cancer prognosis
Authors: Hu Gang , Sun Ningjie , Jiang Jiansong , Chen Xiansheng
Published: September 2020

Background

Gastric cancer (GC) is one of the high-risk cancers that lacks effective methods for prognosis prediction. Therefore, we searched for immune cells related to the prognosis of GC and studied the role of related genes in GC prognosis.

Methods

In this study, we collected the mRNA data of GC from The Cancer Genome Atlas (TCGA) database and studied the immune cells that were closely related to the prognosis of GC. Spearman correlation analysis was performed to show the association between immune cell-related genes and the differentially expressed genes (DEGs) of GC. Univariate and multivariate Cox regression analyses were conducted on the immune cell-related genes with a high correlation with GC. A prognostic risk score model was constructed and the most significant feature genes were identified. Kaplan–Meier method was then used to compare the overall survival (OS) of patients with high-risk and low-risk, and receiver operating characteristic (ROC) analysis was used to assess the accuracy of the risk model. In addition, GC patients were grouped according to the median expression of the features genes, and survival analysis was further carried out.

Results

It was noted that regulatory T cells (Tregs) were significantly correlated with the prognosis of GC, and 172 genes related to Tregs were found to be closely associated with GC. An optimal prognostic risk model was constructed, and a 5-gene (including LRFN4, ADAMTS12, MCEMP1, HP and MUC15) signature-based risk score was established. Survival analysis showed significant difference in OS between low-risk and high-risk samples. ROC analysis results indicated that the risk model had a high accuracy for the prognosis prediction of samples (AUC = 0.717). The results of survival analysis on each feature gene based on expression levels were consistent with the results of multivariate Cox analysis for predicting the risk rate of the 5 genes.

Conclusion

These results proved that the 5-gene signature-based risk score could be used to predict the survival of GC patients, and these 5 genes were closely related to Tregs. These findings are of great significance for studying the role of immune cells and related immune factors in regulating the prognosis of GC.
The relationship between TRAF6 and tumors
Authors: Li Jiaoduan , Liu Nian , Tang Ling , Yan Bei , Chen Xiang , Zhang Jianglin , Peng Cong
Published: September 2020

Tumor necrosis factor receptor (TNFR)-related factors (TRAFs) are important linker molecules in the tumor necrosis factor superfamily (TNFSF) and the Toll-like/interleukin-1 receptor (TLR/ILR) superfamily. There are seven members: TRAF1-TRAF7, among those members, tumor necrosis factor receptor-associated factor 6 (TRAF6) is upregulated in various tumors, which has been related to tumorigenesis and development. With the in-depth study of the relationship between TRAF6 and different types of tumors,TRAF6has oncogenic characteristics involved in tumorigenesis, tumor development, invasion, and metastasis through various signaling pathways, therefore, targeting TRAF6 has provided a novel strategy for tumor treatment. This review summarizes and analyzes the role of TRAF6 in tumorigenesis and tumor development in combination with the current research on TRAF6 and tumors.
circRAE1 promotes colorectal cancer cell migration and invasion by modulating miR-338-3p/TYRO3 axis
Authors: Du Jiabin , Xu Jianhua , Chen Junxing , Liu Weinan , Wang Pengcheng , Ye Kai
Published: September 2020

Background

Growing evidence has revealed the involvement of circular RNAs (circRNAs) in numerous carcinogenesis. However, the role of circRNAs in the cancer biology of colorectal cancer (CRC) remains vague.

Methods

Quantitative RT-PCR was used to detect the expression level of circRAE1 in CRC tissues and CRC cell lines. Cell proliferation, migration, and invasion were detected using CCK8 assay, Colony formation assay, wound-healing and Transwell assays. The interaction between circRAE1 and miR-338-3p and TRYO3 was confirmed using dual-luciferase reporter assays.

Results

We uncovered a novel circRNA Hsa_circ_0060967 (also known as circRAE1) that was remarkably increased in CRC tissues. The high circRAE1 level was positively associated with advanced tumor stage, lymph node metastasis, and tumor size. The loss-of-function assay showed that circRAE1 accelerated cell proliferation, migration, and invasion. Besides, miR-338-3p was lowly expressed in the CRC tissues and CRC cell lines. The dual-luciferase reporter assays showed that circRAE1 could sponge miR-338-3p, which targeted TRYO3 in CRC cells. Furthermore, the overexpression of circRAE1 could rescue the impaired migration and invasion triggered by miR-338-3p mimics or si-TYRO3 in CRC cells and vice versa.

Conclusion

We identified the network of circRAE1, miR-338-3p, and TYRO3 in CRC cells and determined that the increase in circRAE1 could serve as an oncogene by sponging miR-338-3p, which resulted in an upregulated TYRO3 expression. The finding suggests that circRAE1 is a potential therapeutic target and diagnostic marker for CRC treatment.
CircRNA_104889 promotes lung adenocarcinoma cell invasion via sponging miR4458
Authors: Yan Yongyong , Yang Jiantian , Pathak Janak L. , Wang Haiyan , Zha Jun , Wei Yongxiang , Tang Haibo , Ge Linhu
Published: September 2020

Background

Lung adenocarcinoma is metastatic cancer with a high mortality rate. Circular RNAs (circRNAs) are a type of noncoding RNA and play a vital role in cancer progression. However, the expression and function of circRNAs in lung adenocarcinoma are still mostly unknown.

Methods

In this study, we screened the differential expression of circRNAs in human bronchial epithelial cells (HBE) and A549 human lung adenocarcinoma cell line (A549) by human circRNA microarray and RT-qPCR. The role of overexpressed circRNA_104889 in A549 cell proliferation, apoptosis, migration, and invasion was studied extensively. Intracellular localization of circRNA_104889 was visualized by FISH assay. MiRNA sponging, ERK1/2 signaling, and caspase-3 expression were analyzed in siRNA-mediated circRNA_104889 knockdowned A549 cells.

Results

CircRNA microarray showed overexpression of circRNA_104889 (> 13-fold) in A459 cells compared to HBE. This finding was further corroborated by the RT-qPCR result. CircRNA_104889 was mainly localized in the cytoplasm of A549 cells. The knockdown of circRNA_104889 in A549 cells by si-RNA mediated RNA interference did not affect cell proliferation and apoptosis but significantly inhibited cell migration and invasion in vitro. Furthermore, knockdown of circRNA_104889 led to an increase of miR4458 expression. Overexpression of miR4458 inhibited A549 cell migration. Both the knockdown of circRNA_104889 and overexpression of miR4458 inhibited the caspase-3 expression and ERK1/2 phosphorylation in A549 cells.

Conclusions

CircRNA_104889 promotes lung adenocarcinoma cell migration and invasion by sponging miR4458 and targeting ERK1/2 signaling and caspase-3 expression.
Molecular epidemiological surveillance of Africa and Asia imported malaria in Wuhan, Central China: comparison of diagnostic tools during 2011–2018
Authors: Xie Yiting , Wu Kai , Cheng Weijia , Jiang Tingting , Yao Yi , Xu Mingxing , Yang Yan , Tan Huabing , Li Jian
Published: September 2020

Background

Malaria remains a serious public health problem globally. As the elimination of indigenous malaria continues in China, imported malaria has gradually become a major health hazard. Well-timed and accurate diagnoses could support the timely implementation of therapeutic schedules, reveal the prevalence of imported malaria and avoid transmission of the disease.

Methods

Blood samples were collected in Wuhan, China, from August 2011 to December 2018. All patients accepted microscopy and rapid diagnosis test (RDT) examinations. Subsequently, each of the positive or suspected positive cases was tested for four human-infectious Plasmodium species by using 18S rRNA-based nested PCR and Taqman probe-based real-time PCR. The results of the microscopy and the two molecular diagnostic methods were analysed. Importation origins were traced by country, and the prevalence of Plasmodium species was analysed by year.

Results

A total of 296 blood samples, including 288 that were microscopy and RDT positive, 7 RDT and Plasmodium falciparum positive, and 1 suspected case, were collected and reanalysed. After application of the two molecular methods and sequencing, 291 cases including 245 P. falciparum, 15 Plasmodium vivax, 20 Plasmodium ovale, 6 Plasmodium malariae and 5 mixed infections (3 P. falciparum + P. ovale, 2 P. vivax + P. ovale) were confirmed. These patients had returned from Africa (95.53%) and Asia (4.47%). Although the prevalence displayed a small-scale fluctuation, the overall trend of the imported cases increased yearly.

Conclusions

These results emphasize the necessity of combined utilization of the four tools for malaria diagnosis in clinic and in field surveys of potential risk regions worldwide including Wuhan.
The clinical spectrum of severe childhood malaria in Eastern Uganda
Authors: Olupot-Olupot Peter , Engoru Charles , Nteziyaremye Julius , Chebet Martin , Ssenyondo Tonny , Muhindo Rita , Nyutu Gideon , Macharia Alexander W. , Uyoga Sophie , Ndila Carolyne M. , Karamagi Charles , Maitland Kathryn , Williams Thomas N.
Published: September 2020

Background

Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year.

Methods

A prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda. All children aged 2 months–12 years who presented on Mondays to Fridays between 8.00 am and 5.00 pm from 5th May 2011 until 30th April 2012 were screened for parasitaemia. Clinical and laboratory data were then collected from all P. falciparum positive children with features of WHO-defined severe malaria by use of a standardized proforma.

Results

A total of 10 208 children were screened of which 6582 (64%) had a positive blood film. Of these children, 662 (10%) had clinical features of severe malaria and were consented for the current study. Respiratory distress was the most common severity feature (554; 83.7%), while 365/585 (62.4%) had hyperparasitaemia, 177/662 (26.7%) had clinical jaundice, 169 (25.5%) had severe anaemia, 134/660 (20.2%) had hyperlactataemia (lactate ≥ 5 mmol/L), 93 (14.0%) had passed dark red or black urine, 52 (7.9%) had impaired consciousness and 49/662 (7.4%) had hypoxaemia (oxygen saturations < 90%). In-hospital mortality was 63/662 (9.5%) overall but was higher in children with either cerebral malaria (33.3%) or severe anaemia (19.5%). Factors that were independently associated with mortality on multivariate analysis included severe anaemia [odds ratio (OR) 5.36; 2.16–1.32; P = 0.0002], hyperlactataemia (OR 3.66; 1.72–7.80; P = 0.001), hypoxaemia (OR) 3.64 (95% CI 1.39–9.52; P = 0.008), and hepatomegaly (OR 2.29; 1.29–4.06; P = 0.004). No independent association was found between mortality and either coma or hyperparasitaemia.

Conclusions

Severe childhood malaria remains common in Eastern Uganda where it continues to be associated with high mortality. An unusually high proportion of children with severe malaria had jaundice or gave a history of having recently passed dark red or black urine, an issue worthy of further investigation.
Tranexamic acid adverse reactions: a brief summary for internists and emergency doctors
Authors: Murdaca Giuseppe , Greco Monica , Vassallo Chiara , Gangemi Sebastiano
Published: September 2020

Tranexamic acid (TXA) is a synthetic lysine analogue that is well known as antifibrinolytic agent. It can reduce blood loss in clinical use, especially in conditions where fibrinolysis or hyperfibrinolysis are involved, such as trauma or surgery. Moreover, TXA has been approved as second-line prophylactic therapy for hereditary angioedema and further data have been published about a possible use of TXA as maintenance treatment for nonhistaminergic angioedema and treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors. TXA can be administered through several routes: orally, topically, or intravenously. Although, it is a drug with a very high safety profile, in few cases hypersensitivity reactions have been described occurring with different clinical manifestations. Ethamsylate can be an alternative in TXA sensitized patients. In this brief article we describe TXA adverse reactions and current protocols which have been proposed to help clinicians to diagnose TXA hypersensitivity.
Gender differences in quality of life among patients with myasthenia gravis in China
Authors: Dong Dong , Chong Marc Ka-chun , Wu Yushan , Kaminski Henry , Cutter Gary , Xu Xianhao , Li Haifeng , Zhao Chongbo , Yin Jian , Yu Siyue , Zhu Jianfeng
Published: September 2020

Background

Myasthenia gravis (MG), a chronic neuromuscular disorder, can adversely affect patients’ health-related quality of life (HRQoL), especially in women. The study aimed to evaluate the difference in HRQoL of women and men MG patients and explore the factors that mediate the relationship between gender and HRQoL.

Methods

A cross-sectional study was conducted among 1815 patients with MG in China. The revised 15-item MG quality of life scale (MG-QOL15r) was used to access patients’ HRQoL in overall, physical, social and emotional domains. Socio-demographic information, diagnosis and treatment history, comorbidities, social support, active lifestyle and the MG activities of daily living scale (MG-ADL) were recorded and compared between women and men using the Student’s t-test and Pearson’s Chi-square test. Multivariable regression analyses were conducted to identify independent contributors to HRQoL, especially those affecting different gender.

Results

On average, female patients with MG reported a lower MG-QOL15r score than the males (44.49 ± 29.10 vs 49.32 ± 29.18). The association between gender and patients’ HRQoL interacted with the number of comorbidities across the overall, physical and social domains of patients. As the number of comorbidities increased, the scores of HRQoL decreased and it was faster among females than the males (p < 0.05). Moreover, unemployment, exacerbation of the disease, and active lifestyle contributed to the patients’ HRQoL across all domains. Unemployment (β = − 4.99 [95%CI, − 7.80 to − 2.18], p < 0.001) and exacerbations (β = − 8.49 [95%CI, − 11.43 to − 5.54], p < 0.001) were correlated with poorer HRQoL; while an active lifestyle had a positive impact on HRQoL (β = 0.28 [95%CI, 0.16 to 0.40], p < 0.001).

Conclusions

The results indicate that the HRQoL of women MG patients was lower than that of men. The relationship between gender and HRQoL is modulated by the number of comorbidities. Thus, to improve the HRQoL of women MG patients, symptomatic treatments might not be enough, their comorbid conditions should be considered as well. Additionally, employment status, MG exacerbations, and an active lifestyle have been found as determining factors of the patients’ HRQoL, which suggests future interventions should cope with these factors to improve their quality of life.
Immune infiltrating cells in duodenal cancers
Authors: Donisi G. , Capretti G. , Cortese N. , Rigamonti A. , Gavazzi F. , Nappo G. , Pulvirenti A. , Sollai M. , Spaggiari P. , Zerbi A. , Marchesi F.
Published: September 2020

Background

Duodenal adenocarcinoma (DA) is a rare yet aggressive malignancy, with increasing incidence in the last decades. Its low frequency has hampered a thorough understanding of the pathogenesis of the disease and of its biology, limiting the identification of tailored therapeutic options. A large body of evidence has clearly shown the clinical relevance of immune cells in solid tumors, correlating immune features with post-surgical prognosis. The aim of this study was to analyze the immune contexture in a cohort of duodenal adenocarcinomas surgically resected at our Institution and define its correlation with clinical variables.

Methods

Tissue slides from paraffin-embedded tumor specimens of 15 consecutive DA and 3 adenomas that underwent a pancreaticoduodenectomy in our center between 2010 to 2018 were immunohistochemically stained. The density (percentage of immune reactive area, IRA%) of immune markers CD45RO, CD8, CD20, IL-17, PD-1, CD68 was quantified by computer-assisted image analysis. Demographic, clinical, histopathological data were collected.

Results

In our population, median IRA % (IQR) of immune subsets was respectively CD45RO-TILs 2.19 (2.14), CD8-TIL 0.42 (0.81), CD20-TILs 0.22 (0.51), CD20-TLT 2.84 (4.64), CD68-TAM 2.19 (1.56), IL17+ cells 0.39 (0.39), PD1-TILs 0.19 (0.41). The median follow-up was 47.5 (22.4–63.3) months. At statistical analysis, the density of CD8-TILs inversely correlated with lymph node ratio (p = 0.013), number of metastatic lymph nodes (p = 0.019), and was lower in N+ adenocarcinomas compared to N0 (1.07 vs 0.29; p = 0.093), albeit not significantly. Stratifying patients for the N status, the density of CD8-TILs decreased with the increasing of the N stage (p = 0.065) and was lower in patients who experienced recurrence and died for the disease (0.276 vs 0.641; p = 0.044). Notably, also CD68-TAM distribution was different in patients who had recurrence versus patients who did not (1.028 vs 2.276; p = 0.036).

Conclusions

Immune cells showed variable expression in correlation with common prognostic factors, suggesting T cell infiltration may play a protective role towards lymphatic spread of disease and nodal metastatization. Furthermore, T cell density and macrophage infiltration were associated to a lower risk of recurrence and disease related death. A multicentric approach may be indicated to allow analysis of larger cohorts of patients, potentially increasing the power of our observations.
ARID3a expression in human hematopoietic stem cells is associated with distinct gene patterns in aged individuals
Authors: Ratliff Michelle L. , Garton Joshua , James Judith A. , Webb Carol F.
Published: September 2020

Background

Immunologic aging leads to immune dysfunction, significantly reducing the quality of life of the elderly. Aged-related defects in early hematopoiesis result in reduced lymphoid cell development, functionally defective mature immune cells, and poor protective responses to vaccines and pathogens. Despite considerable progress understanding the underlying causes of decreased immunity in the elderly, the mechanisms by which these occur are still poorly understood. The DNA-binding protein ARID3a is expressed in a subset of human hematopoietic progenitors. Inhibition of ARID3a in bulk human cord blood CD34+ hematopoietic progenitors led to developmental skewing toward myeloid lineage at the expense of lymphoid lineage cells in vitro. Effects of ARID3a expression in adult-derived hematopoietic stem cells (HSCs) have not been analyzed, nor has ARID3a expression been assessed in relationship to age. We hypothesized that decreases in ARID3a could explain some of the defects observed in aging.

Results

Our data reveal decreased frequencies of ARID3a-expressing peripheral blood HSCs from aged healthy individuals compared with young donor HSCs. Inhibition of ARID3a in young donor-derived HSCs limits B lineage potential, suggesting a role for ARID3a in B lymphopoiesis in bone marrow-derived HSCs. Increasing ARID3a levels of HSCs from aged donors in vitro alters B lineage development and maturation. Finally, single cell analyses of ARID3a-expressing HSCs from young versus aged donors identify a number of differentially expressed genes in aged ARID3A-expressing cells versus young ARID3A-expressing HSCs, as well as between ARID3A-expressing and non-expressing cells in both young and aged donor HSCs.

Conclusions

These data suggest that ARID3a-expressing HSCs from aged individuals differ at both molecular and functional levels compared to ARID3a-expressing HSCs from young individuals.
Adjust your own oxygen mask before helping those around you: an autoethnography of participatory research
Authors: Steketee Abby M. , Archibald Thomas G. , Harden Samantha M.
Published: September 2020

Background

There is a need to unpack the empirical, practical, and personal challenges within participatory approaches advocated to optimize implementation. The unpredictable, chaotic nature of participatory approaches complicates application of implementation theories, methods, and strategies which do not address researchers’ situatedness within participatory processes. As an implementation scientist, addressing one’s own situatedness through critical reflection is important to unearth how conscious and unconscious approaches, including ontological and epistemological underpinnings, influence the participatory context, process, and outcomes. Therefore, the aim of this exploratory work is to investigate the heretofore blind spot toward the lived experience of implementation researchers within the participatory process.

Methods

We developed an integrated research-practice partnership (IRPP) to inform the implementation of a gestational weight gain (GWG) control program. Within this IRPP, one investigator conducted a 12-month autoethnography. Data collection and triangulation included field notes, cultural artifacts, and systematic timeline tracking. Data analysis included ethnographic-theoretical dialogue and restorying to synthesize key events and epiphanies into a narrative.

Results

Analysis revealed the unpredicted evolution of the GWG program into a maternal health fair and three themes within the researchers’ lived experience: (1) permeable work boundaries, (2) individual and collective blind spots toward the ontological and epistemological underpinnings of implementation paradigms, and (3) maladaptive behaviors seemingly reinforced by the research culture. These themes contributed to the chaos of implementation and to researchers’ experience of inadequate recovery from cognitive, emotional, and practical demands. These themes also demonstrated the importance of contextual factors, subjectivity, and value-based judgments within implementation research.

Conclusion

Building on extant qualitative research guidelines, we suggest that researchers anchor their approach to implementation in reflexivity, intentionally and iteratively reflecting on their own situatedness. Through this autoethnography, we have elucidated several strategies based on critical reflection including examining philosophical underpinnings of research, adopting restorative practices that align with one’s values, and embracing personal presence as a foundation of scientific productivity. Within the predominant (post-) positivism paradigms, autoethnography may be criticized as unscientifically subjective or self-indulgent. However, this work demonstrates that autoethnography is a vehicle for third-person observation and first-person critical reflection that is transformative in understanding and optimizing implementation contexts, processes, and outcomes.
Measurement of sustainment of prevention programs and initiatives: the sustainment measurement system scale
Authors: Palinkas Lawrence A. , Chou Chih-Ping , Spear Suzanne E. , Mendon Sapna J. , Villamar Juan , Brown C. Hendricks
Published: September 2020

Background

Enhancing the sustainability of evidence-based prevention programs for mental and behavioral health requires tools for measuring both sustainability determinants and sustainment outcomes. The aim of this study was to develop the Sustainment Measurement System Scale (SMSS) and to assess its reliability and construct validity for measuring both determinants and outcomes of efforts to sustain prevention programs and initiatives.

Methods

A 42-item scale comprised of items identified from qualitative data collected from 45 representatives of 10 programs and 8 SAMHSA program officers was administered to 186 representatives of 145 programs funded by 7 SAMHSA prevention grant initiatives. Cronbach’s alphas were used to determine inter-item reliability. Convergent validity was assessed by comparisons of a global measure of sustainment with current SAMHSA-funding status and continued operation in the same form. Discriminant validity was assessed by comparisons of sustainability determinants with whether or not the program had undergone adaptations.

Results

Confirmatory factor analysis provided support for a 35-item model fit to the data. Cronbach’s alpha was .84 for the sustainment outcome construct and ranged from .70 to .93 for the sustainability determinant constructs. All of the determinant constructs were significantly associated with sustainment outcome individual and global measures for the entire sample (p < 0.01 to 0.001) and for community-based programs and programs with a substance abuse focus (p < 0.05 to 0.001). Convergent validity was supported by significant associations between the global sustainment measure and current SAMHSA funding status and continued operation in the same form (p < 0.001). Four of the sustainability determinant constructs (responsive to community needs; coalitions, partnerships, and networks; organizational staff capability; and evaluation, feedback, and program outcomes) were also significantly associated with current SAMHSA funding status (p < 0.5 to 0.01). With the exception of organizational staff capability, all sustainability determinants were unrelated to program adaptation as predicted.

Conclusions

The SMSS demonstrated good reliability and convergent and discriminant validity in assessing likelihood of sustainment of SAMHSA funded prevention programs and initiatives. The measure demonstrates potential in identifying predictors of program sustainment and as a tool for enhancing the likelihood of successful sustainment through ongoing evaluation and feedback.
Proximal tibial morphology and risk of posterior tibial cortex impingement in patients with AA-sized Oxford unicompartmental knee arthroplasty tibial implants
Authors: Charng Jiun-Ran , Chen Alvin Chao-Yu , Chan Yi-Shen , Hsu Kuo Yao , Wu Chen-Te
Published: September 2020

Background

In cases of Oxford unicompartmental knee arthroplasty (UKA), an increase in anteroposterior and medial-lateral length is usually disproportional when comparing AA and A-sized tibial components. Asynchronous increments may cause tibial keel impingement leading to complications.

Methods

Radiographic measurements were performed in five patients with AA-sized tibial implants. The posterior cortex of proximal tibia had two angles recorded as ∠ M1 and ∠ M2. The minimum distance between the tibial component keel and outer margin of the posterior tibial cortex (mDKC) was measured, and the correlation between the preoperative posterior slope angle (PSA), ∠ M1, and mDKC was analyzed.

Results

All patients showed an acceptable component positioning. Only one patient had an mDKC of < 4 mm that fulfilled the criteria for the posterior tibial cortex at risk. The patient had an increased PSA and ∠ M1 compared to other patients. A negative correlation was found between preoperative PSA and mDKC (r = − 0.935, p = 0.0193); and ∠ M1 and mDKC (r = − 0.969, p = 0.0032). However, no stem tip pain, periprosthetic fracture, or component loosening were observed.

Conclusions

The distance between the tibial keel and posterior tibial cortex was reduced in AA-sized patients with a large PSA and ∠M1; therefore, the risk of the tibial cortex injury should be considered.
The effects of immediate programmed cryotherapy and continuous passive motion in patients after computer-assisted total knee arthroplasty: a prospective, randomized controlled trial
Authors: Chen Mei-Chu , Lin Chiu-Chu , Ko Jih-Yang , Kuo Feng-Chih
Published: September 2020

Background

The postoperative nursing intervention with immediate cryotherapy and continuous passive motion (CPM) remains elusive regarding the postoperative pain and range of motion (ROM) for patients undergoing computer-assisted total knee arthroplasty (CAS-TKA).

Methods

A prospective, randomized controlled trial with a purposive sampling method was utilized. Sixty patients scheduled for a unilateral CAS-TKA at a medical center were randomly assigned to the intervention group (n = 30) and control group (n = 30). The intervention group applied programed cryotherapy and CPM within 1 h while returning to the ward on the day of surgery, while the control group did not. Data were analyzed using mixed models to compare the numeric rating scale (NRS) for pain, ROM, and swelling at postoperative day (POD) 4.

Results

There was no significant difference in the NRS score between the groups (p = 0.168). The intervention group had significantly higher ROM than the control group (98° vs. 91°, p = 0.004) at POD 4. Although no significant difference in joint swelling was found between groups (p = 0.157), the intervention group had lower mean joint swelling (32.2 cm) than the control group (33.9 cm).

Conclusions

Immediate programmed cryotherapy and continuous passive motion could help to improve ROM quickly after CAS-TKA. It should be incorporated into the daily nursing plan for patients undergoing CAS-TKA.

Trial registration

ClinicalTrials.gov, NCT04136431. Registered 23 October 2019—retrospectively registered
Registries for orphan drugs: generating evidence or marketing tools?
Authors: Hollak Carla E. M. , Sirrs Sandra , van den Berg Sibren , van der Wel Vincent , Langeveld Mirjam , Dekker Hanka , Lachmann Robin , de Visser Saco J.
Published: September 2020

Independent disease registries for pre-and post-approval of novel treatments for rare diseases are increasingly important for healthcare professionals, patients, regulators and the pharmaceutical industry. Current registries for rare diseases to evaluate orphan drugs are mainly set up and owned by the pharmaceutical industry which leads to unacceptable conflicts of interest. To ensure independence from commercial interests, disease registries should be set up and maintained by healthcare professionals and patients. Public funding should be directed towards an early establishment of international registries for orphan diseases, ideally well before novel treatments are introduced. Regulatory bodies should insist on the use of data from independent disease registries rather than company driven, drug-oriented registries.
Diagnosis of FOXG1 syndrome caused by recurrent balanced chromosomal rearrangements: case study and literature review
Authors: Craig Connor P. , Calamaro Emily , Fong Chin-To , Iqbal Anwar M. , Paciorkowski Alexander R. , Zhang Bin
Published: September 2020

Background

The FOXG1 gene plays a vital role in mammalian brain differentiation and development. Intra- and intergenic mutations resulting in loss of function or altered expression of the FOXG1 gene cause FOXG1 syndrome. The hallmarks of this syndrome are severe developmental delay with absent verbal language, post-natal growth restriction, post-natal microcephaly, and a recognizable movement disorder characterized by chorea and dystonia.

Case presentation

Here we describe a case of a 7-year-old male patient found to have a de novo balanced translocation between chromosome 3 at band 3q14.1 and chromosome 14 at band 14q12 via G-banding chromosome and Fluorescence In Situ Hybridization (FISH) analyses. This rearrangement disrupts the proximity of FOXG1 to a previously described smallest region of deletion overlap (SRO), likely resulting in haploinsufficiency.

Conclusions

This case adds to the growing body of literature implicating chromosomal structural variants in the manifestation of this disorder and highlights the vital role of cis-acting regulatory elements in the normal expression of this gene. Finally, we propose a protocol for reflex FISH analysis to improve diagnostic efficiency for patients with suspected FOXG1 syndrome.
1200 high-quality metagenome-assembled genomes from the rumen of African cattle and their relevance in the context of sub-optimal feeding
Authors: Wilkinson Toby , Korir Daniel , Ogugo Moses , Stewart Robert D. , Watson Mick , Paxton Edith , Goopy John , Robert Christelle
Published: September 2020

Background

The Boran (Bos indicus), indigenous Zebu cattle breed from sub-Saharan Africa, is remarkably well adapted to harsh tropical environments. Due to financial constraints and low-quality forage, African livestock are rarely fed at 100% maintenance energy requirements (MER) and the effect of sub-optimal restricted feeding on the rumen microbiome of African Zebu cattle remains largely unexplored. We collected 24 rumen fluid samples from six Boran cattle fed at sub-optimal and optimal MER levels and characterised their rumen microbial composition by performing shotgun metagenomics and de novo assembly of metagenome-assembled genomes (MAGs). These MAGs were used as reference database to investigate the effect of diet restriction on the composition and functional potential of the rumen microbiome of African cattle.

Results

We report 1200 newly discovered MAGs from the rumen of Boran cattle. A total of 850 were dereplicated, and their uniqueness confirmed with pairwise comparisons (based on Mash distances) between African MAGs and other publicly available genomes from the rumen. A genome-centric investigation into sub-optimal diets highlighted a statistically significant effect on rumen microbial abundance profiles and a previously unobserved relationship between whole microbiome shifts in functional potential and taxon-level associations in metabolic pathways.

Conclusions

This study is the first to identify 1200 high-quality African rumen-specific MAGs and provides further insight into the rumen function in harsh environments with food scarcity. The genomic information from the rumen microbiome of an indigenous African cattle breed sheds light on the microbiome contribution to rumen functionality and constitutes a vital resource in addressing food security in developing countries.
Production routes to bio-acetic acid: life cycle assessment
Authors: Budsberg Erik , Morales-Vera Rodrigo , Crawford Jordan T. , Bura Renata , Gustafson Rick
Published: September 2020

Background

Similar to biofuels, numerous chemicals produced from petroleum resources can also be made from biomass. In this research we investigate cradle to biorefinery exit gate life cycle impacts of producing acetic acid from poplar biomass using a bioconversion process. A key step in developing acetic acid for commercial markets is producing a product with 99.8% purity. This process has been shown to be potentially energy intensive and in this work two distillation and liquid–liquid extraction methods are evaluated to produce glacial bio-acetic acid. Method one uses ethyl acetate for extraction. Method two uses alamine and diisobutyl ketone. Additionally two different options for meeting energy demands at the biorefinery are modeled. Option one involves burning lignin and natural gas onsite to meet heat/steam and electricity demands. Option two uses only natural gas onsite to meet heat/steam demands, purchases electricity from the grid to meet biorefinery needs, and sells lignin from the poplar biomass as a co-product to a coal burning power plant to be co-fired with coal. System expansion is used to account for by-products and co-products for the main life cycle assessment. Allocation assessments are also performed to compare the life cycle tradeoffs of using system expansion, mass allocation, or economic allocation for bio-acetic acid production. Finally, a sensitivity analysis is conducted to determine potential effects of a decrease in the fermentation of glucose to acetic acid.

Results

Global warming potential (GWP) and fossil fuel use (FFU) for ethyl acetate extraction range from 1000–2500 kg CO2 eq. and 32–56 GJ per tonne of acetic acid, respectively. Alamine and diisobutyl ketone extraction method GWP and FFU ranges from −370–180 kg CO2 eq. and 15−25 GJ per tonne of acetic acid, respectively.

Conclusions

Overall the alamine/diisobutyl ketone extraction method results in lower GWP and FFU values compared to the ethyl acetate extraction method. Only the alamine/diisobutyl extraction method finds GWP and FFU values lower than those of petroleum based acetic acid. For both extraction methods, exporting lignin as a co-product produced larger GWPs and FFU values compared to burning the lignin at the biorefinery.
Trichinella spiralis co-infection exacerbates Plasmodium berghei malaria-induced hepatopathy
Authors: Mei Xu , Ye Zhanhong , Chang Yuqing , Huang Shiguang , Song Jianping , Lu Fangli
Published: September 2020

Background

AlthoughPlasmodiumparasites and intestinal helminths share common endemic areas, the mechanisms of these co-infections on the host immune response remain not fully understood. Liver involvement in severePlasmodium falciparuminfections is a significant cause of morbidity and mortality. However, the effect of pre-existingTrichinella spiralisinfection on the immune response and liver immune-pathogenesis inP. bergheiANKA (PbANKA)-infected mice needs to be elucidated.

Methods

Outbred Kunming mice were infected withT. spiralisand 9 days later were challenged withP. bergheiANKA (PbANKA), and the investigation occurred at 13 days after co-infection.

Results

Compared withPbANKA-mono-infected mice,T. spiralis+PbANKA-co-infected mice had similar survival rate but lowerPbANKA parasitaemia; however, there were more severe hepatosplenomegaly, increased liver and spleen indexes, and increased liver pathology observed by hematoxylin and eosin staining; higher expression levels of galectin (Gal)-1, Gal-3, CD68+macrophages, and elastase-positive neutrophils measured by immunohistochemical staining; upregulated mRNA expression levels of Gal-1, Gal-3, cytokines (interferon-gamma (IFNγ) and interleukin (IL)-6), and M1 macrophage polarization marker (inducible nitric oxide synthase (iNOS)) in the liver, and increased expression levels of Gal-1, IFNγ, IL-6, eosinophil cationic protein, eosinophil protein X, and M1 (IL-1β and iNOS) and M2 (Ym1) macrophage polarization markers in the spleen of co-infected mice detected by using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).In vitrostudy showed that compared withPbANKA-mono-infected mice, there were significantly increased expression levels of Gal-1, Gal-3, IL-6, IL-1β, and iNOS in the peritoneal macrophage isolated from co-infected mice detected by using qRT-PCR. Correlation analysis revealed significant positive correlations between Gal-3 and IL-1β in the peritoneal macrophages isolated fromPbANKA-mono-infected mice, between Gal-3 and IFNγ in the spleen of co-infected mice, and between Gal-1 and Ym1 in the peritoneal macrophages isolated from co-infected mice.

Conclusions

Our data indicate that pre-existing infection ofT. spiralismay suppressP. bergheiparasitaemia and aggravate malaria-induced liver pathology through stimulating Gal-1 and Gal-3 expression, activating macrophages, neutrophils, and eosinophils, and promoting mediator release and cytokine production.
FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway
Authors: Sun Cheng-Cao , Zhu Wei , Li Shu-Jun , Hu Wei , Zhang Jian , Zhuo Yue , Zhang Han , Wang Juan , Zhang Yu , Huang Shao-Xin , He Qi-Qiang , Li De-Jia
Published: September 2020

Background

Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined.

Methods

qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2.

Results

LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8+ T cell population in LA-4/SLN-205-derived tumors through targeting TGF-β. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83–123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612–727 amino acid [aa]) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel–Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells.

Conclusions

In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.
The Phys-Can observational study: adjuvant chemotherapy is associated with a reduction whereas physical activity level before start of treatment is associated with maintenance of maximal oxygen uptake in patients with cancer
Authors: Wiestad Tor Helge , Raastad Truls , Nordin Karin , Igelström Helena , Henriksson Anna , Demmelmaier Ingrid , Berntsen Sveinung
Published: September 2020

Background

Adjuvant therapy may cause multiple sideeffects on long term health, including reduced cardiorespiratory fitness (CRF) in patients with breast cancer (1, 2). However, there is currently limited knowledge regarding the effect of different types of adjuvant cancer treatment on CRF in other cancer populations. The primary objective of the present study was to assess whether previously known correlates (age, diagnosis, initial CRF, physical activity level), type of adjuvant treatment and cancer-related fatigue were associated with changes in$$ \dot{V}{O}_2\mathit{\max} $$V̇O2maxin patients with breast, prostate or colorectal cancer.

Methods

Prospective study with two time points of assessment, 85 patients scheduled for adjuvant cancer treatment were included. Cardiorespiratory fitness was assessed by$$ \dot{\ V}{O}_2\mathit{\max} $$V̇O2maxduring a maximal incremental exercise test on a treadmill before start of adjuvant therapy and again six months later. Physical activity level was recorded with a physical activity monitor (Sense Wear™ Mini) at baseline as average minutes of moderate-to-vigorous intensity physical activity (MVPA) per day. Physical fatigue at baseline was reported using the Multidimensional Fatigue Inventory-20 questionaire.

Results

In multivariate linear regression analysis, 30 min higher daily MVPA at baseline was associated with a 5% higher$$ \dot{V}{O}_2\mathit{\max} $$V̇O2maxat six months follow up when adjusted for adjuvant treatment (P = 0.010). Patients receiving adjuvant chemotherapy had a mean decline in$$ \dot{V}{O}_2\mathit{\max} $$V̇O2maxof 10% (− 19, − 1; 95% confidence interval) compared to patients receiving adjuvant endocrine treatment (P = 0.028). Adjuvant radiotherapy, fatigue, age and diagnosis were not significantly associated with changes in$$ \dot{V}{O}_2\mathit{\max} $$V̇O2max.

Conclusion

The results of the present study indicate that adjuvant chemotherapy is associated with a subsequent reduction in$$ \dot{V}{O}_2\mathit{\max} $$V̇O2maxin patients with cancer whereas MVPA before start of adjuvant treatment is positively associated with a higher$$ \dot{V}{O}_2\mathit{\max} $$V̇O2maxafter end of adjuvant treatment.
Molecular dynamics simulation and experimental study of the surface-display of SPA protein via Lpp-OmpA system for screening of IgG
Authors: Vahed M. , Ramezani F. , Tafakori V. , Mirbagheri V. S. , Najafi A. , Ahmadian G.
Published: September 2020

Staphylococcal protein A (SpA) is a major virulence factor of Staphylococcus aureus. S. aureus is able to escape detection by the immune system by the surface display of protein A. The SpA protein is broadly used to purify immunoglobulin G (IgG) antibodies. This study investigates the fusion ability of Lpp′-OmpA (46–159) to anchor and display five replicate domains of protein A with 295 residues length (SpA295) of S. aureus on the surface of Escherichia coli to develop a novel bioadsorbent. First, the binding between Lpp’-OmpA-SPA295 and IgGFc and the three-dimensional structure was investigated using molecular dynamics simulation. Then high IgG recovery from human serum by the surface-displayed system of Lpp′-OmpA-SPA295 performed experimentally. In silico analysis was demonstrated the binding potential of SPA295 to IgG after expression on LPP-OmpA surface. Surface-engineered E. coli displaying SpA protein and IgG-binding assay with SDS-PAGE analysis exhibited high potential of the expressed complex on the E. coli surface for IgG capture from human serum which is applicable to conventional immune precipitation.
Task offloading and resource allocation for UAV-assisted mobile edge computing with imperfect channel estimation over Rician fading channels
Authors: Wang Guangying , Yu Xiangbin , Xu Fangcheng , Cai Jiali
Published: September 2020

In this paper, we develop task offloading and resource allocation scheme for unmanned aerial vehicle (UAV)-assisted mobile edge computing (MEC) system with channel estimation errors over Rician fading channels. The objective is to maximize the system utility with constrained network stability, transmit power, and data arrival rate. We consider a general multi-user UAV-assisted MEC system based on frequency division multiple access (FDMA), and we assume that the computation tasks are split into separate tasks and offloaded to the server for computing. We study stochastic computational resource management based on the Lyapunov optimization algorithm. The optimal transmit power and bandwidth allocation for computation offloading are obtained alternately, and the optimal computation task admission at each time slot and the optimal value of the auxiliary variable are derived. Simulation results verify the effectiveness of the proposed scheme in the paper and evaluate the influence of various parameters to the system performance.