bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant therapy for retroperitoneal sarcoma: a meta-analysis
Authors: Li Xiangji , Wu Tong , Xiao Mengmeng , Wu Shanshan , Min Li , Luo Chenghua 
Published: October 2021

Abstract
Background
Adjuvant therapy is a promising treatment to improve the prognosis of cancer patients, however, the evidence base driving recommendations for adjuvant radiotherapy (ART) or chemotherapy (ACT) in retroperitoneal sarcomas (RPS) primarily hinges on observational data. The aim of this study was to evaluate the effectiveness of adjuvant therapy in the management of RPS patients.

Methods
We searched PubMed, Web of Science, Embase, ASCO Abstracts, and Cochrane Library for comparative studies (until December 2020) of adjuvant therapy versus surgery alone. Data on the following endpoints were evaluated: overall survival (OS), local recurrence (LR), recurrence-free survival (RFS), and metastasis-free survival (MFS). Data were summarized as hazard ratios (HR) with 95% confidence intervals (CI). Risk of bias of studies was assessed with Begg’s and Egger’s tests.

Results
A total of 15 trials were eligible, including 9281 adjuvant therapy and 21,583 surgery alone cases (20 studies for OS, six studies for RFS, two studies for LR, and two studies for MFS). Meta-analysis showed that ART was associated with distinct advantages as compared to surgery alone, including a longer OS (HR = 0.80, P < 0.0001), a longer RFS (HR = 0.61, P = 0.0002), and a lower LR (HR = 0.31, P = 0.005). However, this meta-analysis failed to demonstrate a benefit of ACT for RPS patients, including OS (HR = 1.11, P = 0.19), RFS (HR = 1.30, P = 0.09) and MFS (HR = 0.69, P = 0.09). In the sensitivity analysis, ACT was associated with a worse OS (HR = 1.19, P = 0.0002). No evidence of publication bias was observed.

Conclusions
Overall, the quality of the evidence was moderate for most outcomes. The evidence supports that ART achieved a generally better outcome as compared to surgery alone.
Clinicopathologic significance and prognostic value of circRNAs in osteosarcoma: a systematic review and meta-analysis
Authors: Zhong Jingyu , Zhang Guangcheng , Yao Weiwu 
Published: October 2021

Abstract

Background
Osteosarcoma is the most prevalent malignant osseous sarcoma in children and adolescents, whose prognosis is still relatively poor nowadays. Recent studies have shown the critical function and potential clinical applications of circular RNAs (circRNAs) in osteosarcoma. Our review aimed to perform an updated meta-analysis to explore their clinicopathologic significance and prognostic value.

Methods
The structured literature was conducted via eight electronic databases and four gray literature sources until 20 Feb 2021 to identify eligible studies. The data was extracted directly from the articles or reconstructed based on Kaplan-Meier curves. The Newcastle-Ottawa Scale (NOS) tool was used to assess study quality. The clinicopathologic significance of circRNAs was measured through odds ratios (ORs) and their 95% confidence intervals (CIs), while the prognostic value was evaluated through hazard ratios (HRs) and their 95% CIs of overall survival (OS) and disease-free survival (DFS). Heterogeneity and publication bias were assessed. Sensitivity analyses were conducted. Subgroup analyses were performed according to study characteristics. An additional analysis was performed to investigate the relation between circ_0002052 and osteosarcoma.

Results
Fifty-two studies were identified, in which 38 on clinicopathologic features and 36 on survival prognosis were included in quantitative analysis. The overall study quality was moderate with a median NOS score of 5.5 stars (range 3 to 8). For clinicopathologic features, dysregulated circRNAs were related to larger tumor size (OR 2.122, 95%CI 1.418–3.175), advanced clinical stage (OR 2.847, 95%CI 2.059–3.935), and present of metastasis (OR 2.630, 95%CI 1.583–4.371). For chemotherapy, dysregulated circRNAs suggest a better response (OR 0.443, 95%CI 0.231–0.849), but a higher probability of resistance (OR 9.343, 95%CI 5.352–16.309). For survival prognosis, dysregulated circRNAs were significantly correlated with poor OS (HR 2.437, 95%CI 2.224–2.670) and DFS (HR 2.125, 95%CI 1.621–2.786). The results did not show differences among subgroups. Higher circ_0002052 expression showed a relation with poor OS (HR 3.197, 95%CI 2.054–4.976).

Conclusions
Our review demonstrated that abnormally expressed circRNAs have a relation with advanced clinicopathologic features and better response, but a higher probability of resistance and poor survival prognosis in osteosarcoma patients. However, more studies are encouraged to provide more robust evidence to translate circRNAs into clinical practice.

Trial registration
PROSPERO ID: CRD42021235031
Allelic and dosage effects of NHS in X-linked cataract and Nance–Horan syndrome: a family study and literature review
Authors: Miller Caroline , Gertsen Benjamin G. , Schroeder Audrey L. , Fong Chin-To , Iqbal M. Anwar , Zhang Bin 
Published: October 2021

AbstractNance–Horan syndrome (NHS) is a rare X-linked dominant disorder caused by mutation in the NHS gene on chromosome Xp22.13. (OMIM 302350). Classic NHS manifested in males is characterized by congenital cataracts, dental anomalies, dysmorphic facial features and occasionally intellectual disability. Females typically have a milder presentation. The majority of reported cases of NHS are the result of nonsense mutations and small deletions. Isolated X-linked congenital cataract is caused by non-recurrent rearrangement-associated aberrant NHS transcription. Classic NHS in females associated with gene disruption by balanced X-autosome translocation has been infrequently reported. We present a familial NHS associated with translocation t(X;19) (Xp22.13;q13.1). The proband, a 28-year-old female, presented with intellectual disability, dysmorphic features, short stature, primary amenorrhea, cleft palate, and horseshoe kidney, but no NHS phenotype. A karyotype and chromosome microarray analysis (CMA) revealed partial monosomy Xp/partial trisomy 19q with the breakpoint at Xp22.13 disrupting the NHS gene. Family history revealed congenital cataracts and glaucoma in the patient’s mother, and congenital cataracts in maternal half-sister and maternal grandmother. The same balanced translocation t(X;19) was subsequently identified in both the mother and maternal half-sister, and further clinical evaluation of the maternal half-sister made a diagnosis of NHS. This study describes the clinical implication of NHS gene disruption due to balanced X-autosome translocations as a unique mechanism causing Nance–Horan syndrome, refines dose effects of NHS on disease presentation and phenotype expressivity, and justifies consideration of karyotype and fluorescence in situ hybridization (FISH) analysis for female patients with familial NHS if single-gene analysis of NHS is negative.
Mutant NPM1-regulated lncRNA HOTAIRM1 promotes leukemia cell autophagy and proliferation by targeting EGR1 and ULK3
Authors: Jing Yipei , Jiang Xueke , Lei Li , Peng Meixi , Ren Jun , Xiao Qiaoling , Tao Yao , Tao Yonghong , Huang Junpeng , Wang Lu , Tang Yuting , Yang Zailin , Yang Zesong , Zhang Ling 
Published: October 2021

Abstract
Background
Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1), which displays a distinct long noncoding RNA (lncRNA) expression profile, has been defined as a unique subgroup in the new classification of myeloid neoplasms. However, the biological roles of key lncRNAs in the development of NPM1-mutated AML are currently unclear. Here, we aimed to investigate the functional and mechanistic roles of the lncRNA HOTAIRM1 in NPM1-mutated AML.

Methods
The expression of HOTAIRM1 was analyzed with a public database and further determined by qRT-PCR in NPM1-mutated AML samples and cell lines. The cause of upregulated HOTAIRM1 expression was investigated by luciferase reporter, chromatin immunoprecipitation and ubiquitination assays. The functional role of HOTAIRM1 in autophagy and proliferation was evaluated using western blot analysis, immunofluorescence staining, a Cell Counting Kit-8 (CCK-8) assay, a 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, flow cytometric analyses and animal studies. The action mechanism of HOTAIRM1 was explored through RNA fluorescence in situ hybridization, RNA pulldown and RNA immunoprecipitation assays.

Results
HOTAIRM1 was highly expressed in NPM1-mutated AML. High HOTAIRM1 expression was induced in part by mutant NPM1 via KLF5-dependent transcriptional regulation. Importantly, HOTAIRM1 promoted autophagy and proliferation both in vitro and in vivo. Mechanistic investigations demonstrated that nuclear HOTAIRM1 promoted EGR1 degradation by serving as a scaffold to facilitate MDM2-EGR1 complex formation, while cytoplasmic HOTAIRM1 acted as a sponge for miR-152-3p to increase ULK3 expression.

Conclusions
Taken together, our findings identify two oncogenic regulatory axes in NPM1-mutated AML centered on HOTAIRM1: one involving EGR1 and MDM2 in the nucleus and the other involving the miR-152-3p/ULK3 axis in the cytoplasm. Our study indicates that HOTAIRM1 may be a promising therapeutic target for this distinct leukemia subtype.
Global properties of regulatory sequences are predicted by transcription factor recognition mechanisms
Authors: Patel Zain M. , Hughes Timothy R. 
Published: October 2021

Abstract
Background
Mammalian genomes contain millions of putative regulatory sequences, which are delineated by binding of multiple transcription factors. The degree to which spacing and orientation constraints among transcription factor binding sites contribute to the recognition and identity of regulatory sequence is an unresolved but important question that impacts our understanding of genome function and evolution. Global mechanisms that underlie phenomena including the size of regulatory sequences, their uniqueness, and their evolutionary turnover remain poorly described.

Results
Here, we ask whether models incorporating different degrees of spacing and orientation constraints among transcription factor binding sites are broadly consistent with several global properties of regulatory sequence. These properties include length, sequence diversity, turnover rate, and dominance of specific TFs in regulatory site identity and cell type specification. Models with and without spacing and orientation constraints are generally consistent with all observed properties of regulatory sequence, and with regulatory sequences being fundamentally small (~ 1 nucleosome). Uniqueness of regulatory regions and their rapid evolutionary turnover are expected under all models examined. An intriguing issue we identify is that the complexity of eukaryotic regulatory sites must scale with the number of active transcription factors, in order to accomplish observed specificity.

Conclusions
Models of transcription factor binding with or without spacing and orientation constraints predict that regulatory sequences should be fundamentally short, unique, and turn over rapidly. We posit that the existence of master regulators may be, in part, a consequence of evolutionary pressure to limit the complexity and increase evolvability of regulatory sites.
Network propagation-based prioritization of long tail genes in 17 cancer types
Authors: Mohsen Hussein , Gunasekharan Vignesh , Qing Tao , Seay Montrell , Surovtseva Yulia , Negahban Sahand , Szallasi Zoltan , Pusztai Lajos , Gerstein Mark B. 
Published: October 2021

Abstract
Background
The diversity of genomic alterations in cancer poses challenges to fully understanding the etiologies of the disease. Recent interest in infrequent mutations, in genes that reside in the “long tail” of the mutational distribution, uncovered new genes with significant implications in cancer development. The study of cancer-relevant genes often requires integrative approaches pooling together multiple types of biological data. Network propagation methods demonstrate high efficacy in achieving this integration. Yet, the majority of these methods focus their assessment on detecting known cancer genes or identifying altered subnetworks. In this paper, we introduce a network propagation approach that entirely focuses on prioritizing long tail genes with potential functional impact on cancer development.

Results
We identify sets of often overlooked, rarely to moderately mutated genes whose biological interactions significantly propel their mutation-frequency-based rank upwards during propagation in 17 cancer types. We call these sets “upward mobility genes” and hypothesize that their significant rank improvement indicates functional importance. We report new cancer-pathway associations based on upward mobility genes that are not previously identified using driver genes alone, validate their role in cancer cell survival in vitro using extensive genome-wide RNAi and CRISPR data repositories, and further conduct in vitro functional screenings resulting in the validation of 18 previously unreported genes.

Conclusion
Our analysis extends the spectrum of cancer-relevant genes and identifies novel potential therapeutic targets.
The effect of irrigation on malaria vector bionomics and transmission intensity in western Ethiopia
Authors: Haileselassie Werissaw , Zemene Endalew , Lee Ming-Chieh , Zhong Daibin , Zhou Guofa , Taye Behailu , Dagne Alemayehu , Deressa Wakgari , Kazura James W. , Yan Guiyun , Yewhalaw Delenasaw 
Published: October 2021

Abstract
Background
Irrigation schemes may result in subsequent changes in malaria disease dynamics. Understanding the mechanisms and effects of irrigation on malaria vector bionomics and transmission intensity is essential to develop new or alternative surveillance and control strategies to reduce or control malaria risk. This study was designed to assess the effect of rice irrigation on malaria vector bionomics and transmission intensity in the Gambella Region, Ethiopia.

Methods
Comparative cross-sectional study was conducted in Abobo District of the Gambella Region, Ethiopia. Accordingly, clusters (kebeles) were classified into nearby and faraway clusters depending on their proximity to the irrigation scheme. Adult mosquito survey was conducted in February, August and November 2018 from three nearby and three faraway clusters using Centers for Disease Control and Prevention (CDC) light traps (LTs). During the November survey, human landing catch (HLC) and pyrethrum spray catch (PSC) were also conducted. The collected mosquitoes were morphologically identified to species and tested for Plasmodium infection using circumsporozoite protein enzyme-linked immunosorbent assay (CSP-ELISA). Furthermore, species-specific polymerase chain reaction (PCR) was performed to identify member species of the Anopheles gambiae complex. Chi-square and t-tests were used to analyze the data using the SPSS version 20 software package.

Results
A total of 4319 female anopheline mosquitoes comprising An. gambiae sensu lato, An. funestus group, An. pharoensis, An. coustani complex and An. squamosus were collected. Overall, 84.5% and 15.5% of the anopheline mosquitoes were collected from the nearby and faraway clusters, respectively. Anopheles gambiae s.l. was the predominant (56.2%) anopheline species in the area followed by An. pharoensis (15.7%). The density of anopheline mosquitoes was significantly higher in the nearby clusters in both HLCs [t(3)  =  5.14, P  =  0.0143] and CDC LT catches [t(271.97)  =  7.446, P  <  0.0001). The overall sporozoite rate of anopheline species from the nearby clusters was 10-fold higher compared to the faraway clusters.

Conclusions
Significantly higher mosquito population density was observed in areas close to the irrigation sites. Sporozoite infection rate in the mosquito population was also markedly higher from the nearby clusters. Therefore, the irrigation scheme could increase the risk of malaria in the area.

Graphical abstract
Australian mosquito assemblages vary between ground and sub-canopy habitats
Authors: Sebayang Boni F. , Russell Tanya L. , Staunton Kyran M. , Townsend Michael , Paton Christopher , Lehmann Tovi , Burkot Thomas R. 
Published: October 2021

AbstractBackgroundThe surveillance and control of mosquito-borne diseases is dependent upon understanding the bionomics and distribution of the vectors. Most studies of mosquito assemblages describe species abundance, richness and composition close to the ground defined often by only one sampling method. In this study, we assessed Australian mosquito species near the ground and in the sub-canopy using two traps baited with a variety of lures.MethodsMosquitoes were sampled using a 4 × 4 Latin square design at the Cattana Wetlands, Australia from February to April 2020, using passive box traps with octenol and carbon dioxide and three variations of a sticky net trap (unbaited, and baited with octenol or octenol and carbon dioxide). The traps were deployed at two different heights: ground level (≤ 1 m above the ground) and sub-canopy level (6 m above the ground).ResultsIn total, 27 mosquito species were identified across the ground and sub-canopy levels from the different traps. The abundance of mosquitoes at the ground level was twofold greater than at the sub-canopy level. While the species richness at ground and sub-canopy levels was not significantly different, species abundance varied by the collection height.ConclusionsThe composition of mosquito population assemblages was correlated with the trap types and heights at which they were deployed.Coquillettidiaspecies, which prefer feeding on birds, were mainly found in the sub-canopy whereasAnopheles farauti,Aedes vigilaxandMansonia uniformis, which have a preference for feeding on large mammals, were predominantly found near the ground. In addition to trap height, environmental factors and mosquito bionomic characteristics (e.g. larval habitat, resting behaviour and host blood preferences) may explain the vertical distribution of mosquitoes. This information is useful to better understand how vectors may acquire and transmit pathogens to hosts living at different heights.Graphical abstract
Epidemiological features and spatial–temporal distribution of visceral leishmaniasis in mainland China: a population-based surveillance study from 2004 to 2019
Authors: Guan Zhou , Chen Can , Huang Chenyang , Zhang Hongwei , Zhou Yiyi , Zhou Yuqing , Wu Jie , Zhou Zhengbin , Yang Shigui , Li Lanjuan 
Published: October 2021

Abstract
Background
Although visceral leishmaniasis (VL) was largely brought under control in most regions of China during the previous century, VL cases have rebounded in western and central China in recent decades. The aim of this study was to investigate the epidemiological features and spatial–temporal distribution of VL in mainland China from 2004 to 2019.

Methods
Incidence and mortality data for VL during the period 2004–2019 were collected from the Public Health Sciences Data Center of China and annual national epidemic reports of VL, whose data source was the National Diseases Reporting Information System. Joinpoint regression analysis was performed to explore the trends of VL. Spatial autocorrelation and spatial–temporal clustering analysis were conducted to identify the distribution and risk areas of VL transmission.

Results
A total of 4877 VL cases were reported in mainland China during 2004–2019, with mean annual incidence of 0.0228/100,000. VL incidence showed a decreasing trend in general during our study period (annual percentage change [APC] = −4.2564, 95% confidence interval [CI]: −8.0856 to −0.2677). Among mainly endemic provinces, VL was initially heavily epidemic in Gansu, Sichuan, and especially Xinjiang, but subsequently decreased considerably. In contrast, Shaanxi and Shanxi witnessed significantly increasing trends, especially in 2017–2019. The first-level spatial–temporal aggregation area covered two endemic provinces in northwestern China, including Gansu and Xinjiang, with the gathering time from 2004 to 2011 (relative risk [RR] = 13.91, log-likelihood ratio [LLR] = 3308.87, P < 0.001). The secondary aggregation area was detected in Shanxi province of central China, with the gathering time of 2019 (RR = 1.61, LLR = 4.88, P = 0.041). The epidemic peak of October to November disappeared in 2018–2019, leaving only one peak in March to May.

Conclusions
Our findings suggest that VL is still an important endemic infectious disease in China. Epidemic trends in different provinces changed significantly and spatial–temporal aggregation areas shifted from northwestern to central China during our study period. Mitigation strategies, including large-scale screening, insecticide spraying, and health education encouraging behavioral change, in combination with other integrated approaches, are needed to decrease transmission risk in areas at risk, especially in Shanxi, Shaanxi, and Gansu provinces.

Graphical abstract
Chemical composition and the insecticidal activity of Aeollanthus pubescens leaf essential oil against Anopheles gambiae sensu stricto
Authors: Bohounton Roméo Barnabé , Djogbénou Luc Salako , Djihinto Oswald Yédjinnavênan , Dedome Oronce Sedjro-Ludolphe , Sovegnon Pierre Marie , Barea Bruno , Adomou Aristide , Villeneuve Pierre , Tchobo Fidèle Paul 
Published: October 2021

Abstract
Background
The excessive use of synthetic insecticides is responsible for many cases of resistance in insects. Therefore, the use of natural molecules of ecological interest with insecticidal properties is an alternative approach to the use of synthetic insecticides. The aim of this study is to investigating the larvicidal and adulticidal activity and the chemical composition of the essential oil of Aeollanthus pubescens on the major malaria vector, Anopheles gambiae.

Methods
Three reference strains of Anopheles gambiae sensu stricto (Kisumu, Kiskdr and Acerkis) were used in this study. The leaves of A. pubescens were collected in southern Benin. The standard World Health Organisation (WHO) guidelines for larvicide evaluation were used, and the chemical composition of the essential oil was analysed by gas chromatography coupled to mass spectrometry. Adult mosquitoes of each strain were exposed to pieces of net coated with the essential oil for 3 min using the WHO cone bioassay method. Probit regression analysis was used to determine the concentrations that would kill 50 and 95% of each test population (LC50, LC95) and the knockdown time for 50 and 95% of each test population (KDT50, and KDT95). The difference between the mortality–dose regressions for the different strains was analysed using the likelihood ratio test (LRT). The log-rank test was performed to evaluate the difference in survival between the strains.

Results
A total of 14 components were identified, accounting for 98.3% of total oil content. The major components were carvacrol (51.1%), thymyle acetate (14.0%) and ɣ-terpinene (10.6%). The essential oil showed larvicidal properties on the Kisumu, Acerkis and Kiskdr strains, with LC50 of 29.6, 22.9 and 28.4 ppm, respectively. With pieces of netting treated at 165 µg/cm2, the KDT50 of both Acerkis (1.71 s; Z = 3.34, P < 0.001) and Kiskdr (2.67 s; Z = 3.49, P < 0.001) individuals were significantly lower than that of Kisumu (3.8 s). The lifespan of the three mosquito strains decreased to 1 day for Kisumu (χ2 = 99, df = 1, P < 0.001), 2 days for Acerkis (χ2 = 117, df = 1, P < 0.001) and 3 days for Kiskdr (χ2 = 96.9, df = 1, P < 0.001).

Conclusion
Our findings show that A. pubescens essential oil has larvicide and adulticide properties against the malaria vector An. gambiae sensu stricto, suggesting that this essential oil may be a potential candidate for the control of the resistant malaria-transmitting vectors.

Graphical Abstract