bluuebunny/crossref_metadata_2025 huggingface dataset:
Trichostrongyloid nematodes in ruminants of northern Iran: prevalence and molecular analysis
Authors: Hosseinnezhad Hedayat , Sharifdini Meysam , Ashrafi Keyhan , Atrkar Roushan Zahra , Mirjalali Hamed , Rahmati Behnaz
Published: December 2021

Background

This study was carried out to investigate the prevalence and analyze the molecular characteristics based on the internal transcribed spacer (ITS) 2 region of the ribosomal RNA (RNA) gene of trichostrongylid nematodes in different ruminants from Guilan province, northern of Iran.

Methods

The gastrointestinal tracts of 144 ruminants including 72 cattle, 59 sheep, and 13 goats were collected from an abattoir in Guilan province during July to September 2018. After isolation the helminths, male specimens were identified based on morphological parameters. PCR and partial sequencing of the ITS2 fragment were conducted. After phylogenetic analysis, the intraspecific and interspecific differences were calculated.

Results

The prevalence of total infections with the nematodes was 38.9, 74.6 and 84.6% among cattle, sheep and goats, respectively. Eleven species of trichostrongylid nematodes includingHaemonchus contortus,Marshallagia marshalli,Trichostrongylus axei,T. colubriformis,T. vitrinus,Ostertagia trifurcata,Teladorsagia circumcincta,Marshallagia occidentalis,O. lyrata,O. ostertagi, andCooperia punctatewere recovered from the ruminants. The most prevalent trichostrongyloid nematodes in cattle, sheep and goats wereO. ostertagi(26.4%),M. marshalli(64.4%) andT. circumcincta(69.2%), respectively. Phylogenetic tree was discriminative for Trichostrongylidae family, while phylogenetic analysis of the ITS2 gene represented low variations and no species identification of Haemonchidae and Cooperiidae families.

Conclusions

This study suggests the high prevalence and species diversity of trichostrongyloid nematodes in different ruminants, indicating the importance of implement antiparasitic strategies in north regions of Iran. As well, this study showed that the ITS2 fragment is not a discriminative marker for Haemonchidae and Cooperiidae families, and investigation of other genetic markers such as mitochondrial genes would be more valuable for better understanding of their phylogenetic relationships.
Gene biomarker prediction in glioma by integrating scRNA-seq data and gene regulatory network
Authors: Qin Guimin , Du Longting , Ma Yuying , Yin Yu , Wang Liming
Published: December 2021

Background

Although great efforts have been made to study the occurrence and development of glioma, the molecular mechanisms of glioma are still unclear. Single-cell sequencing technology provides a new perspective for researchers to explore the pathogens of tumors to further help make treatment and prognosis decisions for patients with tumors.

Methods

In this study, we proposed an algorithm framework to explore the molecular mechanisms of glioma by integrating single-cell gene expression profiles and gene regulatory relations. First, since there were great differences among malignant cells from different glioma samples, we analyzed the expression status of malignant cells for each sample, and then tumor consensus genes were identified by constructing and analyzing cell-specific networks. Second, to comprehensively analyze the characteristics of glioma, we integrated transcriptional regulatory relationships and consensus genes to construct a tumor-specific regulatory network. Third, we performed a hybrid clustering analysis to identify glioma cell types. Finally, candidate tumor gene biomarkers were identified based on cell types and known glioma-related genes.

Results

We got six identified cell types using the method we proposed and for these cell types, we performed functional and biological pathway enrichment analyses. The candidate tumor gene biomarkers were analyzed through survival analysis and verified using literature from PubMed.

Conclusions

The results showed that these candidate tumor gene biomarkers were closely related to glioma and could provide clues for the diagnosis and prognosis of patients with glioma. In addition, we found that four of the candidate tumor gene biomarkers (NDUFS5, NDUFA1, NDUFA13, and NDUFB8) belong to the NADH ubiquinone oxidoreductase subunit gene family, so we inferred that this gene family may be strongly related to glioma.
Evaluation of the anticarcinogenic potential of the endophyte, Streptomyces sp. LRE541 isolated from Lilium davidii var. unicolor (Hoog) Cotton
Authors: Ma Aiai , Jiang Kan , Chen Bin , Chen Shasha , Qi Xinge , Lu Huining , Liu Junlin , Zhou Xuan , Gao Tan , Li Jinhui , Zhao Changming
Published: December 2021

Background

Endophytic actinomycetes, as emerging sources of bioactive metabolites, have been paid great attention over the years. Recent reports demonstrated that endophytic streptomycetes could yield compounds with potent anticancer properties that may be developed as chemotherapeutic drugs.

Results

Here, a total of 15 actinomycete-like isolates were obtained from the root tissues of Lilium davidii var. unicolor (Hoog) Cotton based on their morphological appearance, mycelia coloration and diffusible pigments. The preliminary screening of antagonistic capabilities of the 15 isolates showed that isolate LRE541 displayed antimicrobial activities against all of the seven tested pathogenic microorganisms. Further in vitro cytotoxicity test of the LRE541 extract revealed that this isolate possesses potent anticancer activities with IC50 values of 0.021, 0.2904, 1.484, 4.861, 6.986, 8.106, 10.87, 12.98, and 16.94 μg/mL against cancer cell lines RKO, 7901, HepG2, CAL-27, MCF-7, K562, Hela, SW1990, and A549, respectively. LRE541 was characterized and identified as belonging to the genus Streptomyces based on the 16S rRNA gene sequence analysis. It produced extensively branched red substrate and vivid pink aerial hyphae that changed into amaranth, with elliptic spores sessile to the aerial mycelia. To further explore the mechanism underlying the decrease of cancer cell viability following the LRE541 extract treatment, cell apoptosis and cell cycle arrest assays were conducted in two cancer cell lines, RKO and 7901. The result demonstrated that LRE541 extract inhibited cell proliferation of RKO and 7901 by causing cell cycle arrest both at the S phase and inducing apoptosis in a dose-dependent manner. The chemical profile of LRE541 extract performed by the UHPLC-MS/MS analysis revealed the presence of thirty-nine antitumor compounds in the extract. Further chemical investigation of the LRE541 extract led to the discovery of one prenylated indole diketopiperazine (DKP) alkaloid, elucidated as neoechinulin A, a known antitumor agent firstly detected in Streptomyces; two anthraquinones 4-deoxy-ε-pyrromycinone (1) and epsilon-pyrromycinone (2) both displaying anticancer activities against RKO, SW1990, A549, and HepG2 with IC50 values of 14.96 ± 2.6 − 20.42 ± 4.24 μg/mL for (1); 12.9 ± 2.13, 19.3 ± 4.32, 16.8 ± 0.75, and 18.6 ± 3.03 μg/mL for (2), respectively.

Conclusion

Our work evaluated the anticarcinogenic potential of the endophyte, Streptomyces sp. LRE541 and obtained one prenylated indole diketopiperazine alkaloid and two anthraquinones. Neoechinulin A, as a known antitumor agent, was identified for the first time in Streptomyces. Though previously found in Streptomyces, epsilon-pyrromycinone and 4-deoxy-ε-pyrromycinone were firstly shown to possess anticancer activities.

Graphical Abstract
Effect of stocking density and age on physiological performance and dynamic gut bacterial and fungal communities in Langya hens
Authors: Wang Yaping , Jin Taihua , Zhang Ningbo , Li Jiongkui , Wang Yan , Kulyar Muhammad Fakhar-e-Alam , Han Zhaoqing , Li Yongzhu
Published: December 2021

Background

The characterization of colonization and dynamic changes related to gut microorganisms might be vital, as it presents an opportunity to quantify the co-variation between stocking densities and gut microbiome of dynamic distribution. The objective of this study was to determine the stocking density on physiological performance and dynamic distribution of gut microbiome (including bacterial and fungal communities) of Langya laying hens in the two development stages.

Methods

A randomized design with 2 × 3 factorial controls consisting of two development stages (24, 43 weeks-old) with three different stocking densities was performed. Three different stocking densities were allocated to a total of 300 11-week-old Langya laying hens (450 cm2/bird, 675 cm2/bird, 900 cm2/bird). Three housing densities were accomplished by raising different chickens per cage with the same floor size. The dependent variables of stocking densities at each sampling point were; growth performance, organs index, egg quality and the changes of dynamic gut bacterial and fungal communities in the cecum.

Results

Results showed that the stocking density didn’t affect liver index, eggshell thickness, breaking shell strength and egg shape index. Hens from the highest stocking density had the lowest body weight, fallopian tube index, egg weight and yolk colour score. Except for the yolk colour score, the measurement changes caused by age followed the opposite pattern as stocking density. We observed a substantial rise in taxa linked with health threats when stocking density was increased, including Talaromyces, Oscillospiraceae_UCG-002, Oscillospira, and Dielma. The opposite was observed with Bacteroides, Bifidobacterium, Lachnoclostridium, Eisenbergiella, and Kurtzmaniella. Also, most taxa were linked to polymicrobial infection in clinical cases, especially species whose percentage declined as the hens aged, such as Terrisporobacter, Faecalicoccus, Dialister, Cylindrocarpon etc. Whereas Sellimonas, Mitsuokella, Eurotium, Wardomyces and Cephalotheca had the opposite trend.

Conclusion

We speculated that excessive high density drove the abundance of bacteria and fungi connected with health problems. Where the gut microecology gradually reach a mature and balance status with age. Overall, this study demonstrates gut microbiome ecological processes in Langya layers at various stocking densities and finds possible connections between stocking density, microbiome and production performance. Our study will contribute to new insights associating suitable density patterns and production performance in laying hens by harnessing such a relative microbiome.
Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: could the combination with other drugs improve its antitumoral effect?
Authors: Escudero Javier , Heredia-Soto Victoria , Wang Yinyin , Ruiz Patricia , Hu Yingying , Gallego Alejandro , Pozo-Kreilinger Jose Juan , Martinez-Marin Virginia , Berjon Alberto , Ortiz-Cruz Eduardo , Bernabeu Daniel , Feliu Jaime , Tang Jing , Redondo Andres , Mendiola Marta
Published: December 2021

Background

Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS).

Methods

In this study, we evaluated the effect of eribulin on proliferation, migration and invasion capabilities in LPS, leiomyosarcoma (LMS) and fibrosarcoma (FS) models, using both monolayer (2D) and three-dimensional (3D) spheroid cell cultures. Additionally, we explored combinations of eribulin with other drugs commonly used in the treatment of STS with the aim of increasing its antitumour activity.

Results

Eribulin showed activity inhibiting proliferation, 2D and 3D migration and invasion in most of the cell line models. Furthermore, we provide data that suggest, for the first time, a synergistic effect with ifosfamide in all models, and with pazopanib in LMS as well as in myxoid and pleomorphic LPS.

Conclusions

Our results support the effect of eribulin on LPS, LMS and FS cell line models. The combination of eribulin with ifosfamide or pazopanib has shown in vitro synergy, which warrants further clinical research.
Long non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis
Authors: Ge Sichen , Jiang Chengyi , Li Min , Cheng Zhongqiang , Feng Xiaojia
Published: December 2021

Background

Previous studies indicated CRNDE to have a pivotal part within tumorigenesis. Notwithstanding, precise details on CRNDE activities within NPC are still uncertain. The investigation described in this article served to focus in greater depth on the mechanistics regarding CRNDE, together with all associated regulatory networks, on nasopharyngeal carcinoma (NPC) and its treatment possibilities.

Methods

Quantitative real-time polymerase chain reaction (RT-qPCR) analyzed CRNDE, miR-545-5p and CCND2 expression within NPCs and representative cell lineages. CCK-8 cell counting-, EdU-, wound-healing-/transwell-assays analyzed cellular proliferation, migrative, together with invasive properties. Apoptosis/cell cycle progression were scrutinized through flow cytometry. Dual-luciferase reporter assays validated CRNDE/miR-545-5p/CCND2 interplay. Proteomic expression of apoptosis-related protein, EMT-related protein and CCND2 protein were evaluated through Western blotting. In addition, Ki67 expression was evaluated through immunohistochemical staining. The effect of CRNDE in vivo was assessed by nude murine xenograft model studies.

Results

This study demonstrated up-regulated expression of CRNDE and CCND2 within NPC tissues/cell lines. Meanwhile, miR-545-5p was down-regulated. CRNDE knock-down or miR-545-5p over-expression drastically reduced NPC proliferative, migrative and invasive properties, promoted apoptosis/altered cell cycle, and inhibited CCND2 expression. However, miR-545-5p down-regulation had opposing effects. All inhibiting functions generated by CRNDE down-regulation upon NPC progression could be counterbalanced or synergistically exacerbated, depending on miR-545-5p down-regulation or up-regulation, respectively. Multiple-level investigations revealed CRNDE to serve as a sponge for miR-545-5p, and can target CCND2 within NPCs.

Conclusions

CRNDE increases CCND2 expression by competitive binding with miR-545-5p, thus accelerating the development of NPC. This provides potential therapeutic targets and prognostic markers against NPC.
Preclinical evaluation of strasseriolides A–D, potent antiplasmodial macrolides isolated from Strasseria geniculata CF-247,251
Authors: Annang Frederick , Pérez-Moreno Guiomar , Díaz Caridad , González-Menéndez Victor , de Pedro Montejo Nuria , del Palacio José Pérez , Sánchez Paula , Tanghe Scott , Rodriguez Ana , Pérez-Victoria Ignacio , Cantizani Juan , Ruiz-Pérez Luis M. , Genilloud Olga , Reyes Fernando , Vicente Francisca , González-Pacanowska Dolores
Published: December 2021

Background

Malaria is a global health problem for which novel therapeutic compounds are needed. To this end, a recently published novel family of antiplasmodial macrolides, strasseriolides A–D, was herein subjected to in vivo efficacy studies and preclinical evaluation in order to identify the most promising candidate(s) for further development.

Methods

Preclinical evaluation of strasseriolides A–D was performed by MTT-based cytotoxicity assay in THLE-2 (CRL-2706) liver cells, cardiotoxicity screening using the FluxOR™ potassium assay in hERG expressed HEK cells, LC–MS-based analysis of drug-drug interaction involving CYP3A4, CYP2D6 and CYP2C9 isoforms inhibition and metabolic stability assays in human liver microsomes. Mice in vivo toxicity studies were also accomplished by i.v. administration of the compounds (vehicle: 0.5% HPMC, 0.5% Tween 80, 0.5% Benzyl alcohol) in mice at 25 mg/kg dosage. Plasma were prepared from mice blood samples obtained at different time points (over a 24-h period), and analysed by LC-MS to quantify compounds. The most promising compounds, strasseriolides C and D, were subjected to a preliminary in vivo efficacy study in which transgenic GFP-luciferase expressing Plasmodium berghei strain ANKA-infected Swiss Webster female mice (n = 4–5) were treated 48 h post-infection with an i.p. dosage of strasseriolide C at 50 mg/kg and strasseriolide D at 22 mg/kg for four days after which luciferase activity was quantified on day 5 in an IVIS® Lumina II imager.

Results

Strasseriolides A–D showed no cytotoxicity, no carditoxicity and no drug-drug interaction problems in vitro with varying intrinsic clearance (CLint). Only strasseriolide B was highly toxic to mice in vivo (even at 1 mg/kg i.v. dosage) and, therefore, discontinued in further in vivo studies. Strasseriolide D showed statistically significant activity in vivo giving rise to lower parasitaemia levels (70% lower) compared to the controls treated with vehicle.

Conclusions

Animal efficacy and preclinical evaluation of the recently discovered potent antiplasmodial macrolides, strasseriolides A–D, led to the identification of strasseriolide D as the most promising compound for further development. Future studies dealing on structure optimization, formulation and establishment of optimal in vivo dosage explorations of this novel compound class could enhance their clinical potency and allow for progress to later stages of the developmental pipeline.
Socioeconomic inequality in congenital heart diseases in Iran
Authors: Amini-Rarani Mostafa , Vahedi Sajad , Borjali Maryam , Nosratabadi Mehdi
Published: December 2021

Introduction

Social-economic factors have an important role in shaping inequality in congenital heart diseases. The current study aimed to assess and decompose the socio-economic inequality in Congenital Heart Diseases (CHDs) in Iran.

Methods

This is a cross-sectional research conducted at Shahid Rajaie Cardiovascular Medical and Research Center in Tehran, Iran, as one of the largest referral heart hospitals in Asia. Data were collected primarily from 600 mothers who attended in pediatric cardiology department in 2020. The polychoric principal component analysis (PCA) and Errygers corrected CI (ECI) were used to construct household socioeconomic status and to assess inequality in CHDs, respectively. A regression-based decomposition analysis was also applied to explain socioeconomic-related inequalities. To select the explanatory social, medical/biological, and lifestyle variables, the chi-square test was first used.

Results

There was a significant pro-rich inequality in CHDs (ECI = -0.65, 95% CI, − 0.72 to − 0.58). The social, medical/biological, and lifestyle variables accounted for 51.47, 43.25, and 3.92% of inequality in CHDs, respectively. Among the social variables, family SES (about 50%) and mother’s occupation (21.05%) contributed the most to CHDs’ inequality. Besides, in the medical/biological group, receiving pregnancy care (22.06%) and using acid folic (15.70%) had the highest contribution.

Conclusion

We concluded that Iran suffers from substantial socioeconomic inequality in CHDs that can be predominantly explained by social and medical/biological variables. It seems that distributional policies aim to reduce income inequality while increasing access of prenatal care and folic acid for disadvantaged mothers could address this inequality much more strongly in Iran.
Domestic and international mobility trends in the United Kingdom during the COVID-19 pandemic: an analysis of facebook data
Authors: Shepherd Harry E. R. , Atherden Florence S. , Chan Ho Man Theophilus , Loveridge Alexandra , Tatem Andrew J.
Published: December 2021

Background

Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of social distancing policies, which resulted in changes to mobility across different regions. An understanding of how these policies impacted travel patterns over time and at different spatial scales is important for designing effective strategies, future pandemic planning and in providing broader insights on the population geography of the country. Crowd level data on mobile phone usage can be used as a proxy for population mobility patterns and provide a way of quantifying in near-real time the impact of social distancing measures on changes in mobility.

Methods

Here we explore patterns of change in densities, domestic and international flows and co-location of Facebook users in the UK from March 2020 to March 2021.

Results

We find substantial heterogeneities across time and region, with large changes observed compared to pre-pademic patterns. The impacts of periods of lockdown on distances travelled and flow volumes are evident, with each showing variations, but some significant reductions in co-location rates. Clear differences in multiple metrics of mobility are seen in central London compared to the rest of the UK, with each of Scotland, Wales and Northern Ireland showing significant deviations from England at times. Moreover, the impacts of rapid changes in rules on international travel to and from the UK are seen in substantial fluctuations in traveller volumes by destination.

Conclusions

While questions remain about the representativeness of the Facebook data, previous studies have shown strong correspondence with census-based data and alternative mobility measures, suggesting that findings here are valuable for guiding strategies.
A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression
Authors: Peng Yin , Xu Yidan , Zhang Xiaojing , Deng Shiqi , Yuan Yuan , Luo Xiaonuan , Hossain Md Tofazzal , Zhu Xiaohui , Du Kaining , Hu Fan , Chen Yang , Chang Shanshan , Feng Xianling , Fan Xinmin , Ashktorab Hassan , Smoot Duane , Meltzer Stephen J. , Hou Gangqiang , Wei Yanjie , Li Song , Qin Ying , Jin Zhe
Published: December 2021

Background

Circular RNA (circRNA), a subclass of non-coding RNA, plays a critical role in cancer tumorigenesis and metastasis. It has been suggested that circRNA acts as a microRNA sponge or a scaffold to interact with protein complexes; however, its full range of functions remains elusive. Recently, some circRNAs have been found to have coding potential.

Methods

To investigate the role of circRNAs in gastric cancer (GC), parallel sequencing was performed using five paired GC samples. Differentially expressed circAXIN1 was proposed to encode a novel protein. FLAG-tagged circRNA overexpression plasmid construction, immunoblotting, mass spectrometry, and luciferase reporter analyses were applied to confirm the coding potential of circAXIN1. Gain- and loss-of-function studies were conducted to study the oncogenic role of circAXIN1 and AXIN1-295aa on the proliferation, migration, invasion, and metastasis of GC cells in vitro and in vivo. The competitive interaction between AXIN1-295aa and adenomatous polyposis coli (APC) was investigated by immunoprecipitation analyses. Wnt signaling activity was observed using a Top/Fopflash assay, real-time quantitative RT-PCR, immunoblotting, immunofluorescence staining, and chromatin immunoprecipitation.

Results

CircAXIN1 is highly expressed in GC tissues compared with its expression in paired adjacent normal gastric tissues. CircAXIN1 encodes a 295 amino acid (aa) novel protein, which was named AXIN1-295aa. CircAXIN1 overexpression enhances the cell proliferation, migration, and invasion of GC cells, while the knockdown of circAXIN1 inhibits the malignant behaviors of GC cells in vitro and in vivo. Mechanistically, AXIN1-295aa competitively interacts with APC, leading to dysfunction of the “destruction complex” of the Wnt pathway. Released β-catenin translocates to the nucleus and binds to the TCF consensus site on the promoter, inducing downstream gene expression.

Conclusion

CircAXIN1 encodes a novel protein, AXIN1-295aa. AXIN1-295aa functions as an oncogenic protein, activating the Wnt signaling pathway to promote GC tumorigenesis and progression, suggesting a potential therapeutic target for GC.
miRNA-214-5p inhibits prostate cancer cell proliferation by targeting SOX4
Authors: Xu Guangchi , Meng Yin , Wang Lihe , Dong Bo , Peng Feifei , Liu Songtao , Li Shukui , Liu Tao
Published: December 2021

Background

Prostate cancer is the most common malignant tumor in men. Due to the lack of theoretical research on its pathogenic mechanism, the current cure rate is still low. miRNAs play an important role in the pathogenesis of various cancers. miRNA-214-5p plays an important role in the development of a variety of cancers. This study aims to explore the expression level of miR-214-5p in prostate cancer and make a preliminary study of its molecular mechanism in the development of prostate cancer to provide effective new strategies for the treatment of prostate cancer.

Methods

The target genes of miRNA-214-5p were predicted with bioinformatics technology, and the target relationship between miRNA-214-5p and its target genes was verified with dual luciferase reporter assay. RT-qPCR and Western blot were used to detect the expression levels of miRNA-214-5p and target genes in 50 clinical samples and two common prostate continuous cell lines, respectively. The targeting relationship between miRNA-214-5p and its target genes was verified with clinical data. miRNA-214-5p and miRNA-214-5p inhibitor was over-expressed in DU-145 cell lines to verify the effect of miRNA-214-5p on prostate cancer cell proliferation and SOX4 gene expression. And the mechanism of miRNA-214-5p inhibiting the proliferation of prostate cancer cells were analyzed by detecting the expression difference of downstream factors of SOX4 pathway. Bioinformatics analysis showed that miRNA-214-5p combined with SOX4 3′UTR region, and dual luciferase reporter assay further verified the reliability of the predicted results. The low expression of miRNA-214-5p was observed in prostate cancer tissues and cells, while high expression of SOX4 was observed in prostate cancer tissues and cells.

Results

Overexpression of miRNA-214-5p to prostate cancer cells significantly inhibited the proliferation of cancer cells, and the expression of SOX4 was inhibited in the transfected cell line. After transfection of miRNA-214-5p inhibitor into prostate cancer cells, the cell proliferation rate further increased. Meanwhile, overexpression of miRNA-214-5p effectively inhibited the expression of SOX4 downstream factors, including c-Myc, eIF4E, and CDK4. However, the specific knockdown of SOX4 through SOX4 shRNA significantly reduced the proliferation of prostate cancer cell lines.

Conclusions

miRNA-214-5 can inhibit the proliferation of prostate cancer cells by specifically targeting S0X4 and inhibiting the expression of growth factors downstream of this pathway.
Endovascular revascularization strategies using catheter-based thrombectomy versus conventional catheter-directed thrombolysis for acute limb ischemia
Authors: Gong Maofeng , He Xu , Zhao Boxiang , Kong Jie , Gu Jianping , Chen Guoping
Published: December 2021

Background

Acute limb ischemia (ALI) is an important clinical event threatening both life and the affected limbs, but the optimal treatment for ALI remains undefined. The aim of this study was to compare the safety and effectiveness of thrombectomy approaches via either catheter-based thrombectomy (CBT) or catheter-directed thrombolysis (CDT).

Methods

A total of 98 patients (mean age 69.7 years, 60 male) who underwent endovascular intervention for ALI from January 2015 to July 2019 were included. Of these, 57 were treated with primary CBT via a large-bore catheter, an AngioJet catheter or Rotarex catheter, and/or underwent low-dose CDT, and 41 were treated with primary CDT. The safety and effectiveness of CBT compared to conventional CDT and other various endovascular techniques were evaluated.

Results

More Rutherford IIb patients were treated with primary CBT (68.4%) than CDT (26.8%; P < .001). Patients who underwent primary CDT achieved a higher technical success rate than those who underwent primary CBT in a shorter procedure time (P < .001), whereas 42.1% of patients who underwent CBT did not need adjunctive CDT. The duration and dosage of adjunctive CDT in the CBT group were significantly decreased compared with those in the primary CDT group (both P < .001), and the CBT group achieved a shorter in-hospital length of stay (P < .001). Subgroup analysis revealed that patients treated with AngioJet and Rotarex catheters achieved slightly lower dosages, shorter CDT durations and shorter in-hospital stay lengths than those treated with large-bore catheters (P > .05). Clinical success was estimated to be achieved in 98.2% of patients who underwent CBT, which is similar to the 97.6% estimated in those who underwent primary CDT (P = 1.000), and this finding was similar among the CBT subgroups. Patients who underwent CBT had a higher procedure-related distal embolization rate and economic cost than those who underwent primary CDT (P < .05), but it had slightly fewer complications than those who underwent primary CDT (P = .059), especially minor complications (P = .036). The freedom from amputation at 6 and 12 months for CBT and CDT was assessed (93.0% vs 90.2% respectively, P = .625; 89.5% vs 82.9%, respectively, P = .34,). Comparable limb salvage was found for different techniques of large bore catheters, AngioJet catheters and Rotarex catheters. The Kaplan-Meier table analysis also showed similar limb salvage rates between groups.

Conclusions

Endovascular treatment of ALI with the use of catheter-based therapies is an effective modality that can reduce the requirement for thrombolysis, with expected reductions in hemorrhagic complications, but at the risk of remediable distal emboli and increased economic cost. It has a similar clinical outcome to conventional CDT alone. Different CBT techniques have comparable efficacy but different adverse event profiles.
First-line pembrolizumab plus chemotherapy for extensive-stage small-cell lung cancer: a United States-based cost-effectiveness analysis
Authors: Zhu Youwen , Hu Huabin , Ding Dong , Li Shuosha , Liao Mengting , Shi Yin , Huang Jin
Published: December 2021

Background

The clinical trial of Keynote-604 showed that pembrolizumab plus chemotherapy could generate clinical benefits for extensive-stage small-cell lung cancer (ES-SCLC). We aim to assess the efficacy and cost of pembrolizumab combined with chemotherapy in the first-line treatment setting of ES-SCLC from the United States (US) payers’ perspective.

Methods

A synthetical Markov model was used to evaluate cost and effectiveness of pembrolizumab plus platinum-etoposide(EP) versus EP in first-line therapy for ES-SCLC from the data of Keynote-604. Lifetime costs life-years(LYs), quality adjusted LYs(QALYs) and incremental cost-effectiveness ratios(ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed. Furthermore, we performed subgroup analysis.

Results

Pembrolizumab plus EP resulted in additional 0.18 QALYs(0.32 LYs) and corresponding incremental costs $113,625, resulting an ICER of $647,509 per QALY versus EP. The price of pembrolizumab had a significant impact on ICER. Probabilistic sensitivity analysis indicated that pembrolizumab combined chemotherapy may become a cost-effective option with a probability of 0%. Besides, subgroup analysis suggested that all subgroups were not cost-effective.

Conclusion

From the perspective of the US payer, pembrolizumab plus EP is not a cost-effective option for first-line treatment patients with ES-SCLC at a WTP threshold of $150,000 per QALY.
Motivational profiles and change in physical activity during a weight loss intervention: a secondary data analysis
Authors: Ostendorf Danielle M. , Schmiege Sarah J. , Conroy David E. , Phelan Suzanne , Bryan Angela D. , Catenacci Victoria A.
Published: December 2021

Background

High levels of moderate-to-vigorous intensity physical activity (MVPA) are strongly associated with sustained weight loss, however the majority of adults are unsuccessful in maintaining high levels of MVPA long-term. Our goal was to identify profiles based on exercise motives, and examine the association between motivational profile and longitudinal changes in MVPA during a weight loss intervention.

Methods

Adults with overweight or obesity (n = 169, mean ± SE; age 39 ± 0.7 years, BMI 34.4 ± 0.3 kg/m2, 83% female) underwent an 18-month behavioral weight loss program, including 6 months of supervised exercise, followed by 6 months of unsupervised exercise. Participants self-reported behavioral regulations for exercise at baseline (BREQ-2). Latent profile analysis identified subgroups from external, introjected, identified, and intrinsic regulations measured at baseline. Mean differences in device-measured total MVPA were compared across motivational profiles at baseline, after 6 months of supervised exercise and after a subsequent 6 months of unsupervised exercise.

Results

Three motivational profiles emerged: high autonomous (high identified and intrinsic, low external regulations; n = 52), high combined (high scores on all exercise regulations; n = 25), and moderate combined (moderate scores on all exercise regulations; n = 92). Motivational profile was not associated with baseline level of MVPA or the increase in MVPA over the 6-month supervised exercise intervention (high autonomous: 21 ± 6 min/d; high combined: 20 ± 9 min/d; moderate combined: 33 ± 5 min/d; overall P > 0.05). However, during the transition from supervised to unsupervised exercise, MVPA decreased, on average, within all three profiles, but the high autonomous profile demonstrated the least attenuation in MVPA (− 3 ± 6 min/d) compared to the moderate combined profile (− 20 ± 5 min/d; P = 0.043).

Conclusions

Results were in alignment with the Self-Determination Theory. Adults motivated by autonomous reasons (value benefits of exercise, intrinsic enjoyment) may be more likely to sustain increases in MVPA once support is removed, whereas participants with moderate-to-high scores on all types of exercise regulations may need additional long-term support in order to sustain initial increases in MVPA.

Clinical trial registration

NCT01985568. Registered 24 October 2013.
Best practices for recruitment of adolescents for biobanking and precision health research: a retrospective analysis comparing juvenile idiopathic arthritis cases with healthy controls
Authors: Lewis Kimberly A. , Brooks Shelby , Carrasco Ruy , Carter Patricia , Garcia Alexandra , Chiou Jennifer , Nguyen Christina , Rana Ambreen , Brown Sharon A. , Tiziani Stefano , Osier Nico
Published: December 2021

Background

Precision health in adolescents relies on the successful collection of data and biospecimens from an adequately sized sample of cases and comparison group(s), often healthy controls, to answer the research question. This research report describes the recruitment strategy, enrollment rates, and approach utilized in a successful biobehavioral research study. The study was designed to examine key health indicators in adolescents (13-17 years of age) with juvenile idiopathic arthritis (JIA) compared to a control group of healthy adolescents. The purpose of this analysis is to establish best practices and identify strategies to overcome barriers to recruitment of older adolescents, an age group that tends to be underrepresented in research studies.

Methods

A retrospective secondary analysis of data from a parent study about JIA with high consent rates was employed to explore factors affecting enrollment into the biobehavioral study.

Results

Of the 113 subjects who were recruited to the study, 74 met the eligibility criteria and reviewed the consent form. The consented group (n=40) represents 54% of those who were eligible upon initial screening. The rate of project enrollment was 2.7 participants per month. The pediatric rheumatologists referred 85% of the JIA group, and the study’s principal investigator, a nurse scientist, referred 95% of the control group. Typical recruitment strategies, such as posting on social media, distributing flyers, and cold-calling potential participants from the clinic schedule were ineffective for both cases and controls. Barriers to enrollment included scheduling and fear of venipuncture. There were no demographic characteristics that significantly explained enrollment, differentiating between those who agreed to participate compared to those who refused. Successful strategies for enrollment of adolescents into this biobehavioral research study included scheduling study visits on weekends and school holidays; an informed consent and assent process that addressed adolescent fears of venipuncture; including a JIA patient on the study team; and utilizing existing relationships to maximize enrollment efforts.

Conclusions

Effective recruitment and enrollment practices were relationship-specific and patient-centered. Researchers should utilize best practices to ensure that precision health for adolescents is advanced.
Adverse events of inactivated COVID-19 vaccine in HIV-infected adults
Authors: Wu Songjie , Zhang Yubin , Ming Fangzhao , Zou Shi , Wu Mengmeng , Guo Wei , Tang Weiming , Liang Ke
Published: December 2021

This study aims to evaluate the safety of inactivated COVID-19 vaccine among adult people living with HIV (PLWH). In total, 259 PLWH who received at least one dose of inactivated COVID-19 vaccine were enrolled, and post-vaccination adverse events (AEs) were evaluated seven days following each vaccination dose. The overall AE frequency was 22.8% after dose one, which was higher than after dose two (10.2%) (P < 0.001). No severe side event or vaccine safety concern was observed. Our finding was essential in reducing vaccine hesitancy among PLWH.
Establishing RNAi for basic research and pest control and identification of the most efficient target genes for pest control: a brief guide
Authors: Mehlhorn Sonja , Hunnekuhl Vera S. , Geibel Sven , Nauen Ralf , Bucher Gregor
Published: December 2021

RNA interference (RNAi) has emerged as a powerful tool for knocking-down gene function in diverse taxa including arthropods for both basic biological research and application in pest control. The conservation of the RNAi mechanism in eukaryotes suggested that it should—in principle—be applicable to most arthropods. However, practical hurdles have been limiting the application in many taxa. For instance, species differ considerably with respect to efficiency of dsRNA uptake from the hemolymph or the gut. Here, we review some of the most frequently encountered technical obstacles when establishing RNAi and suggest a robust procedure for establishing this technique in insect species with special reference to pests. Finally, we present an approach to identify the most effective target genes for the potential control of agricultural and public health pests by RNAi.
Changing the preschool setting to promote healthy energy balance-related behaviours of preschoolers: a qualitative and quantitative process evaluation of the SuperFIT approach
Authors: van de Kolk Ilona , Gerards Sanne , Verhees Anke , Kremers Stef , Gubbels Jessica
Published: December 2021

Background

The Early Care and Education (ECE) setting plays an important role in the promotion of a healthy lifestyle in young children. SuperFIT is a comprehensive, integrated intervention approach designed to promote healthy energy balance-related behaviours in preschoolers. Insight in the process of implementation and the context in which SuperFIT was implemented supports the understanding of how the intervention works in practice. This process evaluation examined factors that influenced the implementation and maintenance, as well as the (perceived) changes in the ECE setting.

Methods

A mixed-methods study was conducted. SuperFIT was implemented at twelve preschools in the south of the Netherlands. The process evaluation was performed among preschool teachers, managers of the preschool organisation, and implementers. Semi-structured in-depth (group) interviews, quantitative process questionnaires, the Child-care Food and Activity Practices Questionnaire (CFAPQ) and the Environmental and Policy Assessment and Observation (EPAO) were used to evaluate the implementation and maintenance of SuperFIT and the changes in the preschool setting. The interviews were analysed using a theoretical framework based on the Implementation Framework of Fleuren and Damschröder’s Consolidated Framework for Implementation Research. Descriptive analyses were performed on the quantitative data.

Results

Various intervention activities were implemented in the preschool setting. Although the intention to maintain SuperFIT was present, this was hindered by time constraints and lack of financial resources. Important factors that influenced implementation and maintenance were incongruence with current practice, limited perceived capabilities to integrate SuperFIT in daily practice, group composition at the preschools, and the perceived top-down implementation. Organizational vision and societal attention regarding healthy behaviour in general were perceived to be supportive for implementation and maintenance. Predominantly, favourable changes were seen in the nutrition- and physical activity-related practices of preschool teachers and other aspects of the social preschool environment such as the use of play materials. Limited changes were observed in the physical preschool environment.

Conclusions

Several factors influenced the implementation and maintenance of SuperFIT in the preschool setting. Some factors evolved over time from hindering to facilitating, emphasising the importance of allowing sufficient time for intervention implementation. SuperFIT changed mainly the social preschool environment.

Trial registration

Clinicaltrials.gov, NCT03021980, date registered: January 16, 2017, prospectively registered
Testing the agreement of trees with internal labels
Authors: Fernández-Baca David , Liu Lei
Published: December 2021

Background

A semi-labeled tree is a tree where all leaves as well as, possibly, some internal nodes are labeled with taxa. Semi-labeled trees encompass ordinary phylogenetic trees and taxonomies. Suppose we are given a collection$${\mathcal {P}}= \{{\mathcal {T}}_1, {\mathcal {T}}_2, \ldots , {\mathcal {T}}_k\}$$P={T1,T2,…,Tk}of semi-labeled trees, called input trees, over partially overlapping sets of taxa. The agreement problem asks whether there exists a tree$${\mathcal {T}}$$T, called an agreement tree, whose taxon set is the union of the taxon sets of the input trees such that the restriction of$${\mathcal {T}}$$Tto the taxon set of$${\mathcal {T}}_i$$Tiis isomorphic to$${\mathcal {T}}_i$$Ti, for each$$i \in \{1, 2, \ldots , k\}$$i∈{1,2,…,k}. The agreement problems is a special case of the supertree problem, the problem of synthesizing a collection of phylogenetic trees with partially overlapping taxon sets into a single supertree that represents the information in the input trees. An obstacle to building large phylogenetic supertrees is the limited amount of taxonomic overlap among the phylogenetic studies from which the input trees are obtained. Incorporating taxonomies into supertree analyses can alleviate this issue.

Results

We give a$${\mathcal {O}}(n k (\sum _{i \in [k]} d_i + \log ^2(nk)))$$O(nk(∑i∈[k]di+log2(nk)))algorithm for the agreement problem, wherenis the total number of distinct taxa in$${\mathcal {P}}$$P,kis the number of trees in$${\mathcal {P}}$$P, and$$d_i$$diis the maximum number of children of a node in$${\mathcal {T}}_i$$Ti.

Conclusion

Our algorithm can aid in integrating taxonomies into supertree analyses. Our computational experience with the algorithm suggests that its performance in practice is much better than its worst-case bound indicates.
Tendon healing is adversely affected by low-grade inflammation
Authors: Chisari Emanuele , Rehak Laura , Khan Wasim S. , Maffulli Nicola
Published: December 2021

Background

Tendinopathy is common, presents with pain and activity limitation, and is associated with a high risk of recurrence of the injury. Tendinopathy usually occurs as a results of a disrupted healing response to a primary injury where cellular and molecular pathways lead to low grade chronic inflammation.

Main findings

There has been a renewed interest in investigating the role of Inflammation in the pathogenesis of tendinopathy, in particular during the initial phases of the condition where it may not be clinically evident. Understanding the early and late stages of tendon injury pathogenesis would help develop new and effective treatments addressed at targeting the inflammatory pathways.

Conclusion

This review outlines the role of low-grade Inflammation in the pathogenesis of tendinopathy, stressing the role of proinflammatory cytokines, proteolytic enzymes and growth factors, and explores how Inflammation exerts a negative influence on the process of tendon healing.
Rhizoma drynariae total flavonoids combined with calcium carbonate ameliorates bone loss in experimentally induced Osteoporosis in rats via the regulation of Wnt3a/β-catenin pathway
Authors: Hu Yimei , Mu Panyun , Ma Xu , Shi Jingru , Zhong Zhendong , Huang Lingyuan
Published: December 2021

Background

Rhizoma drynariae, a traditional Chinese herb, is commonly used in treatment of bone healing in osteoporotic fractures. However, whether theRhizoma drynariaetotal flavonoids (RDTF) can promote the absorption of calcium and enhance the bone formation is unclear. The aim of the present study was to investigate the preventive effects of RDTF combined with calcium carbonate (CaCO3) on estrogen deficiency-induced bone loss.

Methods

Three-month-old Sprague–Dawley rats were ovariectomized (OVX) and then treated with CaCO3,RDTF, and their admixtures for ten weeks, respectively. The bone trabecular microstructure, bone histopathological examination, and serum biomarkers of bone formation and resorption were determined in the rat femur tissue. The contents of osteoprotegerin (OPG), receptor activator of the NF-κB (RANK), and its ligand (RANKL) in marrow were analyzed by ELISA, and the protein expressions of Wnt3a, β-catenin, and phosphorylated β-catenin (p-β-catenin) were analyzed by Western blot. Statistical analysis was conducted by using one-way analysis of variance (ANOVA) followed by LSD post hoc analysis or independent samples t test using the scientific statistic software SPSS version 20.0

Results

RDTF combined with CaCO3could promote osteosis and ameliorate bone loss to improve the repair of cracked bone trabeculae of OVX rats. Furthermore, RDTF combined with CaCO3also could prevent OVX-induced decrease in collagen fibers in the femoral tissue of ovariectomized rats and promote the regeneration of new bone or cartilage tissue, while CaCO3supplementation promoted the increase in bone mineral content. Nevertheless, there was no difference in the expression of Wnt3a, β-catenin and p-β-catenin between osteopenic rats and RDTF treated rats, but RDTF combined with CaCO3could activate the Wnt3a/β-catenin pathway.

Conclusions

RDTF combined with CaCO3could ameliorate estrogen deficiency-induced bone loss via the regulation of Wnt3a/β-catenin pathway.