bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between remnant lipoprotein cholesterol and central systolic blood pressure in a Chinese community-based population: a cross-sectional study
Authors: Li Kaiyin , Fan Fangfang , Zheng Bo , Jia Jia , Liu Bo , Liu Jiahui , Chen Chuyun , Zhou Jing , Zhang Yan , Huo Yong
Published: June 2021

Background

The lipid profile is reportedly related to peripheral blood pressure or pulse wave velocity. However, no studies have investigated the associations between lipid parameters, especially remnant lipoprotein cholesterol (RLP-C), and central systolic blood pressure (cSBP).

Methods

This study used baseline data of a community-based cohort in Beijing, China. Participants who had been treated with anti-hypertensive or lipid-lowering agents were excluded. RLP-C is equal to total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). An Omron HEM-9000AI device was used to measure non-invasive cSBP. The associations between blood lipid profile and non-invasive cSBP were evaluated using multivariable regression models.

Results

The 5173 included participants were 55.0 ± 8.5 years old; 35.7% (1845) of participants were men. Increased cSBP was significantly associated with increased TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), and RLP-C but with decreased HDL-C, even after adjusting for possible covariates. When simultaneously entering individual pairs of RLP-C and other blood lipid parameters into the multivariable regression model, RLP-C remained significantly associated with cSBP, even after adjusting for other lipids. Compared with participants who had RLP-C levels in the first quartile (Q1), cSBP for those with RLP-C in Q4 was increased to 4.57 (95% confidence interval [CI]: 3.08–6.06) mmHg after adjusting for LDL-C, 4.50 (95%CI: 2.98–6.02) mmHg after adjusting for TC, 3.91 (95%CI: 1.92–5.89) mmHg after adjusting for TG, 5.15 (95%CI: 3.67–6.63) mmHg after adjusting for HDL-C, and 4.10 (95%CI: 2.36–5.84) mmHg after adjusting for non-HDL-C.

Conclusions

Increased blood RLP-C level was significantly associated with higher cSBP in a Chinese population, independently of other lipids, which indicates its importance in individual cardiovascular risk assessment.
LED control of gene expression in a nanobiosystem composed of metallic nanoparticles and a genetically modified E. coli strain
Authors: Aratboni Hossein Alishah , Rafiei Nahid , Khorashad Larousse Khosravi , Lerma-Escalera Albert Isaac , Balderas-Cisneros Francisco de Jesús , Liu Zhaowei , Alemzadeh Abbas , Shaji Sadasivan , Morones-Ramírez José Ruben
Published: June 2021

Background

Within the last decade, genetic engineering and synthetic biology have revolutionized society´s ability to mass-produce complex biological products within genetically-modified microorganisms containing elegantly designed genetic circuitry. However, many challenges still exist in developing bioproduction processes involving genetically modified microorganisms with complex or multiple gene circuits. These challenges include the development of external gene expression regulation methods with the following characteristics: spatial–temporal control and scalability, while inducing minimal permanent or irreversible system-wide conditions. Different stimuli have been used to control gene expression and mitigate these challenges, and they can be characterized by the effect they produce in the culture media conditions. Invasive stimuli that cause permanent, irreversible changes (pH and chemical inducers), non-invasive stimuli that cause partially reversible changes (temperature), and non-invasive stimuli that cause reversible changes in the media conditions (ultrasound, magnetic fields, and light).

Methods

Opto-control of gene expression is a non-invasive external trigger that complies with most of the desired characteristics of an external control system. However, the disadvantage relies on the design of the biological photoreceptors and the necessity to design them to respond to a different wavelength for every bioprocess needed to be controlled or regulated in the microorganism. Therefore, this work proposes using biocompatible metallic nanoparticles as external controllers of gene expression, based on their ability to convert light into heat and the capacity of nanotechnology to easily design a wide array of nanostructures capable of absorbing light at different wavelengths and inducing plasmonic photothermal heating.

Results

Here, we designed a nanobiosystem that can be opto-thermally triggered using LED light. The nanobiosystem is composed of biocompatible gold nanoparticles and a genetically modified E. coli with a plasmid that allows mCherry fluorescent protein production at 37 °C in response to an RNA thermometer.

Conclusions

The LED-triggered photothermal protein production system here designed offers a new, cheaper, scalable switchable method, non-destructive for living organisms, and contribute toward the evolution of bioprocess production systems.
Dipstick proteinuria and risk of type 2 diabetes mellitus: a nationwide population-based cohort study
Authors: Jeon Jimin , Kim Jinkwon
Published: June 2021

Background

Proteinuria has been recognized as a marker of systemic inflammation and endothelial dysfunction associated with insulin resistance and β-cell impairment, which can contribute to the development of type 2 diabetes mellitus (T2DM). However, it is unknown whether the dipstick proteinuria test has a predictive value for new-onset T2DM.

Methods

This retrospective cohort study analyzed 239,287 non-diabetic participants who participated in the Korean nationwide health screening program in 2009–2010. Proteinuria was determined by the urine dipstick test at the baseline health screening. We performed multivariate Cox proportional regression analyses for the development of new-onset T2DM. Follow-up was performed until December 2015.

Results

During the mean follow-up period of 5.73 years, 22,215 participants were diagnosed with new-onset T2DM. The presence of proteinuria was significantly associated with an increased risk of T2DM (adjusted hazard ratio: 1.19, 95% confidence interval: 1.10, 1.29). There was a positive dose–response relationship between the degree of dipstick proteinuria and T2DM risk. This significant association between proteinuria and T2DM risk was consistent regardless of the fasting glucose level at baseline.

Conclusions

Dipstick proteinuria is a significant risk factor for new-onset T2DM. Therefore, proteinuria might be a useful biomarker to identify those at a high risk for developing T2DM.
Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients
Authors: Zhang Wei , Lin Liewen , Xia Ligang , Cai Wanxia , Dai Weier , Zou Chang , Yin Lianghong , Tang Donge , Xu Yong , Dai Yong
Published: June 2021

Background

The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. However, no prognostic biomarker has been applied for colorectal cancer (CRC) in the clinic.

Methods

Integrated with transcriptomic data from public databases, multi-omics examinations were conducted to search prognostic biomarkers for CRC. Moreover, the potential biological functions and regulatory mechanism of these predictive genes were also explored.

Results

In this study, we revealed that three mitochondrial genes were associated with the poor prognosis of CRC. Integrated analyses of transcriptome and proteome of CRC patients disclosed numerous down-regulated mitochondrial genes at both mRNA and protein levels, suggesting a vital role of mitochondria in carcinogenesis. Combined with the bioinformatics studies of transcriptomic datasets of 538 CRC patients, three mitochondrial prognostic genes were eventually selected out, including HIGD1A, SUCLG2, and SLC25A24. The expression of HIGD1A exhibited a significant reduction in two subtypes of adenoma and six subtypes of CRC, while the down-regulation of SUCLG2 and SLC25A24 showed more advantages in rectal mucinous adenocarcinoma. Moreover, we unveiled that these three genes had common expressions and might collaboratively participate in the synthesis of ribosomes. Our original multi-omics datasets, including DNA methylation, structural variants, chromatin accessibility, and phosphoproteome, further depicted the altered modifications on their potential transcriptional factors.

Conclusions

In summary, HIGD1A, SUCLG2, and SLC25A24 might serve as predictive biomarkers for CRC. The biological activities they involved in and their upstream regulators we uncovered would provide a functional context for the further-in-depth mechanism study.

Graphic abstract
Large-scale literature mining to assess the relation between anti-cancer drugs and cancer types
Authors: Bauer Chris , Herwig Ralf , Lienhard Matthias , Prasse Paul , Scheffer Tobias , Schuchhardt Johannes
Published: June 2021

Background

There is a huge body of scientific literature describing the relation between tumor types and anti-cancer drugs. The vast amount of scientific literature makes it impossible for researchers and physicians to extract all relevant information manually.

Methods

In order to cope with the large amount of literature we applied an automated text mining approach to assess the relations between 30 most frequent cancer types and 270 anti-cancer drugs. We applied two different approaches, a classical text mining based on named entity recognition and an AI-based approach employing word embeddings. The consistency of literature mining results was validated with 3 independent methods: first, using data from FDA approvals, second, using experimentally measured IC-50 cell line data and third, using clinical patient survival data.

Results

We demonstrated that the automated text mining was able to successfully assess the relation between cancer types and anti-cancer drugs. All validation methods showed a good correspondence between the results from literature mining and independent confirmatory approaches. The relation between most frequent cancer types and drugs employed for their treatment were visualized in a large heatmap. All results are accessible in an interactive web-based knowledge base using the following link: https://knowledgebase.microdiscovery.de/heatmap.

Conclusions

Our approach is able to assess the relations between compounds and cancer types in an automated manner. Both, cancer types and compounds could be grouped into different clusters. Researchers can use the interactive knowledge base to inspect the presented results and follow their own research questions, for example the identification of novel indication areas for known drugs.
Factors affecting the duration of coronary artery lesions in patients with the Kawasaki disease: a retrospective cohort study
Authors: Zhang Xuting , He Yuee , Shao Yiping , Hang Biyao , Xu Zhipeng , Chu Maoping
Published: June 2021

Background

Coronary artery lesions (CALs) are the most severe complication of Kawasaki disease (KD). Approximately 9–20% of the patients with KD develop CAL despite receiving regular treatment (intravenous immunoglobulin [IVIG] and aspirin). Some patients develop coronary aneurysms, leading to coronary artery stenosis or thrombosis, resulting in ischaemic heart disease and significantly affect the patients’ lives. The purpose of this study was to investigate the factors associated with the duration of CAL in patients with KD.

Methods

The data of 464 patients with KD and CAL admitted to the Children’s Heart Centre, The Second Affiliated Hospital and Yuying Children’s Hospital from 2010 to 2018 were retrospectively analysed. Demographic and clinical information and echocardiographic follow-up data were collected. Kaplan–Meier curves were used to estimate the overall CAL duration, and the log-rank test was used to compare statistical differences. Univariate and multivariate Cox regression models were used to identify variables related to the CAL duration.

Results

The median CAL duration was 46 days (95% confidence interval: 41–54 days). CALs were observed in 61.5, 41.5, 33.3, 22.3, 10.3, and 7.7% of the patients at 1 month, 2 months, 3 months, 6 months, 1 year, and 2 years after the onset of KD, respectively. Univariate Cox regression model showed that sex (p = 0.016), rash symptoms (p = 0.035), delayed IVIG treatment (p = 0.022), CAL type (p < 0.001), degree of CAL (p < 0.001), white blood cell count before IVIG treatment (p = 0.019), and platelet count after IVIG treatment (p = 0.003) were statistically significant factors associated with the overall CAL duration. Multivariable Cox regression showed that delayed IVIG treatment (p = 0.020), multiple dilatations (p < 0.001), a greater degree of dilatation (p < 0.001), and higher platelet count after IVIG treatment (p = 0.007) were positively related to CAL duration.

Conclusions

CAL duration was affected by delayed IVIG treatment, type of CAL, degree of CAL, and platelet count after IVIG treatment. These factors should be monitored carefully during the follow-up and management of patients with KD and CAL.
Chinese women’s attitudes towards postpartum interventions to prevent type 2 diabetes after gestational diabetes: a semi-structured qualitative study
Authors: Shang Jie , Henry Amanda , Zhang Puhong , Chen Huan , Thompson Kelly , Wang Xiaodong , Liu Na , Zhang Jiani , Liu Yan , Jin Jianbo , Pan Xiongfei , Yang Xue , Hirst Jane E.
Published: June 2021

Background

Gestational diabetes (GDM) is a global problem affecting millions of pregnant women, including in mainland China. These women are at high risk of Type II diabetes (T2DM). Cost-effective and clinically effective interventions are needed. We aimed to explore Chinese women’s perspectives, concerns and motivations towards participation in early postpartum interventions and/or research to prevent the development of T2DM after a GDM-affected pregnancy.

Methods

We conducted a qualitative study in two hospitals in Chengdu, Southwest China. Face-to-face semi-structured interviews were conducted with 20 women with recent experience of GDM: 16 postpartum women and 4 pregnant women. Women were asked about their attitudes towards postpartum screening for type 2 diabetes, lifestyle interventions, mHealth delivered interventions and pharmacologic interventions (specifically metformin). An inductive approach to analysis was used. Interviews were recorded, transcribed, and coded using NVivo 12 Pro.

Results

Most women held positive attitudes towards participating in T2DM screening, and were willing to participate in postpartum interventions to prevent T2DM through lifestyle change or mHealth interventions. Women were less likely to agree to pharmacological intervention, unless they had family members with diabetes or needed medication themselves during pregnancy. We identified seven domains influencing women’s attitudes towards future interventions: (1) experiences with the health system during pregnancy; (2) living in an enabling environment; (3) the experience of T2DM in family members; (4) knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions, and (7) lifestyle constraints. Those with more severe GDM, an enabling environment and health knowledge, and with experience of T2DM in family members expressed more favourable views of postpartum interventions and research participation to prevent T2DM after GDM. Those who perceived themselves as having mild GDM and those with time/lifestyle constraints were less likely to participate.

Conclusions

Women with experiences of GDM in Chengdu are generally willing to participate in early postpartum interventions and/or research to reduce their risk of T2DM, with a preference for non-drug, mHealth based interventions, integrating lifestyle change strategies, blood glucose monitoring, postpartum recovery and mental health.
Efficient translation of Eggplant mottled dwarf nucleorhabdovirus N and X genes requires both 5′ and 3′ UTRs
Authors: Babaei Ghobad , Massah Amir , Koohi Habibi Mina
Published: June 2021

Background

Circularization of RNA mediated by association of translation factors and RNA elements in 5′ and 3′ UTRs is a common feature for translation control in eukaryotes. There is no information about translation in plant rhabdoviruses and little information is known in animal rhabdoviruses.

Methods

The role of 5′ and 3′ UTRs in two genes of EMDV in translation were studied using luciferase constructs and RNA structures of these sequences were analyzed by SHAPE and Inline probing.

Results

We have found that efficient translation of N and X mRNAs of nucleorhabdovirus Eggplant mottled dwarf virus (EMDV) requires elements present in both 5′ and 3′ UTRs. Luciferase reporter constructs containing precise 5′ and 3′ UTRs of the N and X genes had substantially higher translational activity compared with constructs containing only the 5′ or 3′ UTR. The 3′UTR of carmovirus Turnip crinkle virus, which contains a well-characterized cap-independent translation enhancer, was unable to complement the lack of EMDV 3′ UTR. Addition of cap analog to luciferase constructs containing the UTRs of the N gene did not restore translation, and translation of the reporter construct in the absence of the 5′ cap was higher than the capped construct. No RNA-RNA interactions between 5′ and 3′ UTRs were detected by EMSA or in-line cleavage structural assays. Deletion of 11 nucleotides from the 3′ terminus negated the synergistic activity of the 3′UTR.

Conclusions

The results with RNA-RNA interaction suggesting that translational synergy between the UTRs may utilize alternative means. Mutation analysis in 3′UTR suggesting that the polyadenylation signal sequence contained in this location may play a critical role in translation.
Hybrid emergency rooms reduce the requirement of blood transfusion in patients with severe trauma
Authors: Watanabe Hiroaki , Matsumoto Ryo , Kuramoto Shunsuke , Muronoi Tomohiro , Oka Kazuyuki , Shimojo Yoshihide , Kidani Akihiko , Hira Eiji , Kawamura Toshihiko
Published: June 2021

Background

A hybrid emergency room (ER) is defined as an emergency unit with four functions—performing resuscitation, computed tomography (CT), surgery, and angiography. However, the safety and efficacy of performing CT in a hybrid ER are unclear in primary surveys. Therefore, this study aimed to evaluate the safety and clinical effects of hybrid ERs.

Methods

This retrospective observational study used data from the Shimane University Hospital Trauma Database from January 2016 to February 2019. Hospitalized patients with severe trauma and an injury severity score of ≥ 16 were divided into the non-hybrid ER group (n = 134) and the hybrid ER group (n = 145). The time from arrival to CT and interventions and the number of in-hospital survivors, preventable trauma deaths (PTD), and unexpected survivors (US) were assessed in both groups. Further, the amount of blood transfused was compared between the groups using propensity score matching.

Results

The time from arrival to CT and interventions was significantly reduced in the hybrid ER group compared to that in the non-hybrid ER group (25 vs. 6 min;p< 0.0001 and 101 vs. 41 min;p= 0.0007, respectively). There was no significant difference in the rate of in-hospital survivors (96.9% vs. 96.3%; p = 0.770), PTD (0% vs. 0%), and US (9.0 vs. 6.2%; p = 0.497) between the groups. The amount of blood transfused was significantly lower in the hybrid ER group than in the non-hybrid ER group (whole blood 14 vs. 8,p= 0.004; red blood cell 6 vs. 2,p= 0.012; fresh frozen plasma 9 vs. 6,p= 0.021). This difference was maintained after propensity score matching (whole blood 28 [10–54] vs. 6 [4–16.5],p= 0.015; RBC 8 [2.75–26.5] vs. 2 [0–8.5],p= 0.020, 18 [5.5–27] vs. 6 [3.5–7.5],p= 0.057).

Conclusions

The study results suggest that trauma treatment in a hybrid ER is as safe as conventional treatment performed in a non-hybrid ER. Further, hybrid ERs, which can reduce the time for trauma surveys and treatment, do not require patient transfer and can reduce the amount of blood transfused during resuscitation.
A novel retractor-assisted closed reduction combined with percutaneous pinning fixation for the treatment of elderly distal radius fractures: a retrospective cohort study
Authors: Zhao Bin , Zhao Wenqian , Assan Isaac , Li Zhenji , Bi Rongxiu
Published: June 2021

Background

Percutaneous pinning fixation (PCP) has been used for the treatment of distal radius fractures for decades, especially in the elderly with fragile soft tissue. However, achieving and maintaining a sound anatomic reduction before PCP is difficult if we use the manipulative reduction method alone. Our study innovatively applied the Steinmann pin retractor for closed reduction combined with PCP, to provide a new protocol for the treatment of distal radius fractures.

Methods

From March 2017 to July 2018, 49 patients out of 57 that met the inclusion criteria but not the exclusion criteria were included in our retrospective cohort study. Sixteen patients were treated with Steinmann pin retractor-assisted closed reduction combined with PCP (S-PCP), and 19 patients were treated with the manipulative reduction combined with PCP (M-PCP), and 14 patients were treated with the manipulative reduction combined with cast splint (M-C). All these patients received a positive postoperative radiological and clinical evaluation.

Results

All the patients were followed up for a minimum of 2 years. The radiological parameters in each group improved significantly postoperative (posttreatment). In the S-PCP group, the values of radial height (postoperative, 13.33±1.74 mm; the first follow-up, 13.27±1.81mm; last follow-up, 13.16±1.76mm) and ulnar variance (postoperative, −0.10±1.29mm; the first follow-up, −0.05±1.27mm; last follow-up, −0.12±1.09mm) significantly improved as compared to the M-PCP and M-C groups. While the patients in the M-C group experienced significant re-displacement at the first and last follow-ups, in the S-PCP group, the range of wrist motion including extension (89.94±5.21%), radial deviation (90.69±6.01%), and supination (90.25±5.87%); ulnar deviation (89.81±5.82%) and QuickDASH score (2.70±3.64); and grip strength (92.50±5.59%), pronation (90.50±6.04%), and modified Mayo wrist score (90.94±4.17, the excellent rate reached up to 75%) also improved as compared to the M-PCP group, M-C group, or both groups at the last follow-up.

Conclusion

S-PCP improves fracture reduction and wrist function and can serve as an effective method for A2(AO/OTA) and A3 type of distal radius fractures in the elderly with limited dorsal comminution, including intra-articular fractures with displacement less than 2mm.
Pharmacological rescue of cognitive function in a mouse model of chemobrain
Authors: Nguyen Lien D. , Fischer Tom T. , Ehrlich Barbara E.
Published: June 2021

Background

After chemotherapy, many cancer survivors suffer from long-lasting cognitive impairment, colloquially known as “chemobrain.” However, the trajectories of cognitive changes and the underlying mechanisms remain unclear. We previously established paclitaxel-induced inositol trisphosphate receptor (InsP3R)-dependent calcium oscillations as a mechanism for peripheral neuropathy, which was prevented by lithium pretreatment. Here, we investigated if a similar mechanism also underlay paclitaxel-induced chemobrain.

Method

Mice were injected with 4 doses of 20 mg/kg paclitaxel every other day to induced cognitive impairment. Memory acquisition was assessed with the displaced object recognition test. The morphology of neurons in the prefrontal cortex and the hippocampus was analyzed using Golgi-Cox staining, followed by Sholl analyses. Changes in protein expression were measured by Western blot.

Results

Mice receiving paclitaxel showed impaired short-term spatial memory acquisition both acutely 5 days post injection and chronically 23 days post injection. Dendritic length and complexity were reduced in the hippocampus and the prefrontal cortex after paclitaxel injection. Concurrently, the expression of protein kinase C α (PKCα), an effector in the InsP3R pathway, was increased. Treatment with lithium before or shortly after paclitaxel injection rescued the behavioral, cellular, and molecular deficits observed. Similarly, memory and morphological deficits could be rescued by pretreatment with chelerythrine, a PKC inhibitor.

Conclusion

We establish the InsP3R calcium pathway and impaired neuronal morphology as mechanisms for paclitaxel-induced cognitive impairment. Our findings suggest lithium and PKC inhibitors as candidate agents for preventing chemotherapy-induced cognitive impairment.
Adult neurogenesis mediates forgetting of multiple types of memory in the rat
Authors: Scott Gavin A. , Terstege Dylan J. , Roebuck Andrew J. , Gorzo Kelsea A. , Vu Alex P. , Howland John G. , Epp Jonathan R.
Published: June 2021

The formation and retention of hippocampus-dependent memories is impacted by neurogenesis, a process that involves the production of new neurons in the dentate gyrus of the hippocampus. Recent studies demonstrate that increasing neurogenesis after memory formation induces forgetting of previously acquired memories. Neurogenesis-induced forgetting was originally demonstrated in mice, but a recent report suggests that the same effect may be absent in rats. Although a general species difference is possible, other potential explanations for these incongruent findings are that memories which are more strongly reinforced become resilient to forgetting or that perhaps only certain types of memories are affected. Here, we investigated whether neurogenesis-induced forgetting occurs in rats using several hippocampus-dependent tasks including contextual fear conditioning (CFC), the Morris Water Task (MWT), and touchscreen paired associates learning (PAL). Neurogenesis was increased following training using voluntary exercise for 4 weeks before recall of the previous memory was assessed. We show that voluntary running causes forgetting of context fear memories in a neurogenesis-dependent manner, and that neurogenesis-induced forgetting is present in rats across behavioral tasks despite differences in complexity or reliance on spatial, context, or object memories. In addition, we asked whether stronger memories are less susceptible to forgetting by varying the strength of training. Even with a very strong training protocol in the CFC task, we still observed enhanced forgetting related to increased neurogenesis. These results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories.
Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression
Authors: Kemper Marius , Schiecke Alina , Maar Hanna , Nikulin Sergey , Poloznikov Andrey , Galatenko Vladimir , Tachezy Michael , Gebauer Florian , Lange Tobias , Riecken Kristoffer , Tonevitsky Alexander , Aigner Achim , Izbicki Jakob , Schumacher Udo , Wicklein Daniel
Published: June 2021

Background

Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis.

Methods

Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated.

Results

The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients.

Conclusion

Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA.
p38β - MAPK11 and its role in female cancers
Authors: Katopodis Periklis , Kerslake Rachel , Zikopoulos Athanasios , Beri Nefeli , Anikin Vladimir
Published: June 2021

Background

The p38MAPK family of Mitogen Activated Protein Kinases are a group of signalling molecules involved in cell growth, survival, proliferation and differentiation. The widely studied p38α isoform is ubiquitously expressed and is implicated in a number of cancer pathologies, as are p38γ and p38δ. However, the mechanistic role of the isoform, p38β, remains fairly elusive. Recent studies suggest a possible role of p38β in both breast and endometrial cancer with research suggesting involvement in bone metastasis and cancer cell survival. Female tissue specific cancers such as breast, endometrial, uterine and ovary account for over 3,000,000 cancer related incidents annually; advancements in therapeutics and treatment however require a deeper understanding of the molecular aetiology associated with these diseases. This study provides an overview of the MAPK signalling molecule p38β (MAPK11) in female cancers using anin-silicoapproach.

Methods

A detailed gene expression and methylation analysis was performed using datasets from cBioportal, CanSar and MEXPRESS. Breast, Uterine Endometrial, Cervical, Ovarian and Uterine Carcinosarcoma TCGA cancer datasets were used and analysed.

Results

Data using cBioportal and CanSAR suggest that expression of p38β is lower in cancers: BRCA, UCEC, UCS, CESC and OV compared to normal tissue. Methylation data from SMART and MEXPRESS indicate significant probe level variation of CpG island methylation status of the gene MAPK11. Analysis of the genes’ two CpG islands shows that the gene was hypermethylated in the CpG1 with increased methylation seen in BRCA, CESC and UCEC cancer data sets with a slight increase of expression recorded in cancer samples. CpG2 exhibited hypomethylation with no significant difference between samples and high levels of expression. Further analysis from MEXPRESS revealed no significance between probe methylation and altered levels of expression. In addition, no difference in the expression of BRCA oestrogen/progesterone/HER2 status was seen.

Conclusion

This data provides an overview of the expression of p38β in female tissue specific cancers, showing a decrease in expression of the gene in BRCA, UCEC, CESC, UCS and OV, increasing the understanding of p38β MAPK expression and offering insight for future in-vitro investigation and therapeutic application.
Diaphragm thickening fraction predicts noninvasive ventilation outcome: a preliminary physiological study
Authors: Mercurio Giovanna , D’Arrigo Sonia , Moroni Rossana , Grieco Domenico Luca , Menga Luca Salvatore , Romano Anna , Annetta Maria Giuseppina , Bocci Maria Grazia , Eleuteri Davide , Bello Giuseppe , Montini Luca , Pennisi Mariano Alberto , Conti Giorgio , Antonelli Massimo
Published: June 2021

Background

A correlation between unsuccessful noninvasive ventilation (NIV) and poor outcome has been suggested in de-novo Acute Respiratory Failure (ARF) patients. Consequently, it is of paramount importance to identify accurate predictors of NIV outcome. The aim of our preliminary study is to evaluate the Diaphragmatic Thickening Fraction (DTF) and the respiratory rate/DTF ratio as predictors of NIV outcome in de-novo ARF patients.

Methods

Over 36 months, we studied patients admitted to the emergency department with a diagnosis of de-novo ARF and requiring NIV treatment. DTF and respiratory rate/DTF ratio were measured by 2 trained operators at baseline, at 1, 4, 12, 24, 48, 72 and 96 h of NIV treatment and/or until NIV discontinuation or intubation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of DTF and respiratory rate/DTF ratio to distinguish between patients who were successfully weaned and those who failed.

Results

Eighteen patients were included. We found overall good repeatability of DTF assessment, with Intra-class Correlation Coefficient (ICC) of 0.82 (95% confidence interval 0.72–0.88). The cut-off values of DTF for prediction of NIV failure were < 36.3% and < 37.1% for the operator 1 and 2 (p < 0.0001), respectively. The cut-off value of respiratory rate/DTF ratio for prediction of NIV failure was > 0.6 for both operators (p < 0.0001).

Conclusion

DTF and respiratory rate/DTF ratio may both represent valid, feasible and noninvasive tools to predict NIV outcome in patients with de-novo ARF.

Trial registration ClinicalTrials.gov Identifier: NCT02976233, registered 26 November 2016.
Recommendations for designing and analysing multi-arm non-inferiority trials: a review of methodology and current practice
Authors: Emmerson Jake , Todd Susan , Brown Julia M.
Published: June 2021

Background and purpose

Multi-arm non-inferiority (MANI) trials, here defined as non-inferiority trials with multiple experimental treatment arms, can be useful in situations where several viable treatments exist for a disease area or for testing different dose schedules. To maintain the statistical integrity of such trials, issues regarding both design and analysis must be considered, from both the multi-arm and the non-inferiority perspectives. Little guidance currently exists on exactly how these aspects should be addressed and it is the aim of this paper to provide recommendations to aid the design of future MANI trials.

Methods

A comprehensive literature review covering four databases was conducted to identify publications associated with MANI trials. Literature was split into methodological and trial publications in order to investigate the required design and analysis considerations for MANI trials and whether they were being addressed in practice.

Results

A number of issues were identified that if not properly addressed, could lead to issues with the FWER, power or bias. These ranged from the structuring of trial hypotheses at the design stage to the consideration of potential heterogeneous treatment variances at the analysis stage. One key issue of interest was adjustment for multiple testing at the analysis stage. There was little consensus concerning whether more powerful p value adjustment methods were preferred to approximate adjusted CIs when presenting and interpreting the results of MANI trials.

We found 65 examples of previous MANI trials, of which 31 adjusted for multiple testing out of the 39 that were adjudged to require it. Trials generally preferred to utilise simple, well-known methods for study design and analysis and while some awareness was shown concerning FWER inflation and choice of power, many trials seemed not to consider the issues and did not provide sufficient definition of their chosen design and analysis approaches.

Conclusions

While MANI trials to date have shown some awareness of the issues raised within this paper, very few have satisfied the criteria of the outlined recommendations. Going forward, trials should consider the recommendations in this paper and ensure they clearly define and reason their choices of trial design and analysis techniques.
Ephedra alata fruit extracts: phytochemical screening, anti-proliferative activity and inhibition of DPPH, α-amylase, α-glucosidase, and lipase enzymes
Authors: Jaradat Nidal , Dacca Hanaa , Hawash Mohammed , Abualhasan Murad N.
Published: June 2021

Background

Discovering and screening for potential anti-obesity, anti-diabetic, anticancer, and antioxidant treatments from natural products still in recent times the main goal for many pharmaceutical scientists. The present investigation aimed to evaluate the chemical constituents of Ephedra alata fruits various extracts and to assess their antioxidant, antiobesity, antidiabetic, and cytotoxic effects.

Result

In this work, high content of flavonoids and phenols were observed in the methanol fraction of E. alata fruits, which reached 98.95 mg of RUE/g and 33.22 mg of GAE/g, respectively. The methanol fraction has significant inhibitory activity against DPPH, α-amylase, α-glucosidase, and lipase with an IC50 value of 1.07, 9.43, 46.16, and 66.48 µg/mL. respectively. Also has anticancer activity against HeLa cancer cell line. While the acetone fraction has potent antioxidant activity with IC50 5 µg/mL.

Conclusion

The DPPH and digestive enzymes assays results showed that the methanolic fraction of E. alata fruits has potent antioxidant, anti-diabetic, and anti-obesity activities, which can be an excellent candidate for biological and chemical analysis and can be further subjected for isolation of the therapeutically active compounds with anticancer potency.
Integrated NIRS and QTL assays reveal minor mannose and galactose as contrast lignocellulose factors for biomass enzymatic saccharification in rice
Authors: Hu Zhen , Wang Youmei , Liu Jingyuan , Li Yuqi , Wang Yanting , Huang Jiangfeng , Ai Yuanhang , Chen Peng , He Yuqing , Aftab Muhammad Nauman , Wang Lingqiang , Peng Liangcai
Published: June 2021

Background

Identifying lignocellulose recalcitrant factors and exploring their genetic properties are essential for enhanced biomass enzymatic saccharification in bioenergy crops. Despite genetic modification of major wall polymers has been implemented for reduced recalcitrance in engineered crops, it could most cause a penalty of plant growth and biomass yield. Alternatively, it is increasingly considered to improve minor wall components, but an applicable approach is required for efficient assay of large population of biomass samples. Hence, this study collected total of 100 rice straw samples and characterized all minor wall monosaccharides and biomass enzymatic saccharification by integrating NIRS modeling and QTL profiling.

Results

By performing classic chemical analyses and establishing optimal NIRS equations, this study examined four minor wall monosaccharides and major wall polymers (acid-soluble lignin/ASL, acid-insoluble lignin/AIL, three lignin monomers, crystalline cellulose), which led to largely varied hexoses yields achieved from enzymatic hydrolyses after two alkali pretreatments were conducted with large population of rice straws. Correlation analyses indicated that mannose and galactose can play a contrast role for biomass enzymatic saccharification at P < 0.0 l level (n = 100). Meanwhile, we found that the QTLs controlling mannose, galactose, lignin-related traits, and biomass saccharification were co-located. By combining NIRS assay with QTLs maps, this study further interpreted that the mannose-rich hemicellulose may assist AIL disassociation for enhanced biomass enzymatic saccharification, whereas the galactose-rich polysaccharides should be effectively extracted with ASL from the alkali pretreatment for condensed AIL association with cellulose microfibrils.

Conclusions

By integrating NIRS assay with QTL profiling for large population of rice straw samples, this study has identified that the mannose content of wall polysaccharides could positively affect biomass enzymatic saccharification, while the galactose had a significantly negative impact. It has also sorted out that two minor monosaccharides could distinctively associate with lignin deposition for wall network construction. Hence, this study demonstrates an applicable approach for fast assessments of minor lignocellulose recalcitrant factors and biomass enzymatic saccharification in rice, providing a potential strategy for bioenergy crop breeding and biomass processing.
Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus
Authors: Spadar Anton , Phelan Jody E. , Benavente Ernest Diez , Campos Monica , Gomez Lara Ferrero , Mohareb Fady , Clark Taane G. , Campino Susana
Published: June 2021

Mosquitoes of the genus Aedes are the main vectors of many viruses, e.g. dengue and Zika, which affect millions of people each year and for which there are limited treatment options. Understanding how Aedes mosquitoes tolerate high viral loads may lead to better disease control strategies. Elucidating endogenous viral elements (EVEs) within vector genomes may give exploitable biological insights. Previous studies have reported the presence of a large number of EVEs in Aedes genomes. Here we investigated if flavivirus EVEs are conserved across populations and different Aedes species by using ~ 500 whole genome sequence libraries from Aedes aegypti and Aedes albopictus, sourced from colonies and field mosquitoes across continents. We found that nearly all flavivirus EVEs in the Ae. aegypti reference genome originate from four separate putative viral integration events, and that they are highly conserved across geographically diverse samples. By contrast, flavivirus EVEs in the Ae. albopictus reference genome originate from up to nine distinct integration events and show low levels of conservation, even within samples from narrow geographical ranges. Our analysis suggests that flaviviruses integrated as long sequences and were subsequently fragmented and shuffled by transposable elements. Given that EVEs of Ae. aegypti and Ae. albopictus belong to different phylogenetic clades and have very differing levels of conservation, they may have different evolutionary origins and potentially different functional roles.

Graphical Abstract
Trends in taxonomy of Triatomini (Hemiptera, Reduviidae, Triatominae): reproductive compatibility reinforces the synonymization of Meccus Stål, 1859 with Triatoma Laporte, 1832
Authors: Cesaretto Natália Regina , de Oliveira Jader , Ravazi Amanda , Madeira Fernanda Fernandez , dos Reis Yago Visinho , de Oliveira Ana Beatriz Bortolozo , Vicente Roberto Dezan , Cristal Daniel Cesaretto , Galvão Cleber , de Azeredo-Oliveira Maria Tercília Vilela , da Rosa João Aristeu , Alevi Kaio Cesar Chaboli
Published: June 2021

Background

Meccus' taxonomy has been quite complex since the first species of this genus was described by Burmeister in 1835 as Conorhinus phyllosoma. In 1859 the species was transferred to the genus Meccus and in 1930 to Triatoma. However, in the twentieth century, the Meccus genus was revalidated (alteration corroborated by molecular studies) and, in the twenty-first century, through a comprehensive study including more sophisticated phylogenetic reconstruction methods, Meccus was again synonymous with Triatoma. Events of natural hybridization with production of fertile offspring have already been reported among sympatric species of the T. phyllosoma subcomplex, and experimental crosses demonstrated reproductive viability among practically all species of the T. phyllosoma subcomplex that were considered as belonging to the genus Meccus, as well as between these species and species of Triatoma. Based on the above, we carried out experimental crosses between T. longipennis (considered M. longipennis in some literature) and T. mopan (always considered as belonging to Triatoma) to evaluate the reproductive compatibility between species of the T. phyllosoma complex. In addition, we have grouped our results with information from the literature regarding crosses between species that were grouped in the genus Meccus with Triatoma, in order to discuss the importance of experimental crosses to confirm the generic reorganization of species.

Results

The crosses between T. mopan female and T. longipennis male resulted in viable offspring. The hatching of hybrids, even if only in one direction and/or at low frequency, demonstrates reproductive compatibility and homeology between the genomes of the parents.

Conclusion

Considering that intergeneric crosses usually do not result in viable offspring in Triatominae, the reproductive compatibility observed between the T. phyllosoma subcomplex species considered in the Meccus genus with species of the Triatoma genus shows that there is “intergeneric” genomic compatibility, which corroborates the generic reorganization of Meccus in Triatoma.

Graphical Abstract
Severe hemoperitoneum resulting from restart of letrozole after oocyte retrieval procedure: a case report
Authors: Huang Haipeng , Takai Yasushi , Samejima Kouki , Gomi Yosuke , Narita Tatsuya , Ichinose Shunichiro , Itaya Yukiko , Ono Yosihisa , Matsunaga Sigetaka , Saitoh Masahiro , Seki Hiroyuki
Published: June 2021

Background

In the field of oncofertility, patients with breast cancer are often administered letrozole as an adjuvant drug before and after oocyte retrieval to prevent an increase in circulating estradiol.

Case presentation

We report a case of abdominal hemorrhage due to an ovarian rupture in a 29-year-old Japanese patient who restarted letrozole 2 days after an oocyte retrieval procedure in which 14 mature oocytes were retrieved. The patient had sought embryo cryopreservation as a fertility preservation option before undergoing treatment for recurrent breast cancer. A day after restarting letrozole treatment, the patient unexpectedly developed severe abdominal pain. Laparoscopic hemostasis was performed to manage the ovarian swelling and hemorrhage.

Conclusions

The ovaries can be restimulated by restart letrozole after an oocyte retrieval procedure. Therefore, reproductive-medicine practitioners should understand the potential complications of letrozole administration in such cases and take steps to ensure that they are minimized.