bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract IA017: Synthetic dependencies arising during tumor evolution
Authors: Wood Kris C.
Published: June 2024

Our research focuses on defining tumor-selective survival dependencies and understanding how these dependencies change during tumor evolution. In this talk, I will provide an overview of our lab’s work, highlighting recent and ongoing studies uncovering mechanism-based synthetic lethalities arising in residual and fully drug resistant tumors whose therapeutic exploitation has the potential to select against the most aggressive forms of disease.

Citation Format: Kris C. Wood. Synthetic dependencies arising during tumor evolution [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA017.
Abstract IA021: Environmental challenge rewires functional connections among human genes
Authors: Gilbert Luke , Herken Ben
Published: June 2024

A fundamental question in biology is how a limited number of genes combinatorially govern cellular responses to environmental changes. While the prevailing hypothesis is that relationships between genes, processes, and ontologies could be plastic to achieve this adaptability, quantitatively comparing human gene functional connections between specific environmental conditions at scale is very challenging. Therefore, it remains unclear whether and how human genetic interaction networks are rewired in response to changing environmental conditions. Here, we developed a framework for mapping context-specific genetic interactions, enabling us to measure the plasticity of human genetic architecture upon environmental challenge for ∼250,000 interactions, using cell cycle interruption, genotoxic perturbation, and nutrient deprivation as archetypes. We discover large-scale rewiring of human gene relationships across conditions, highlighted by dramatic shifts in the functional connections of epigenetic regulators (TIP60), cell cycle regulators (PP2A), and glycolysis metabolism. Our study demonstrates that upon environmental perturbation, intra-complex genetic rewiring is rare while inter-complex rewiring is common, suggesting a modular and flexible evolutionary genetic strategy that allows a limited number of human genes to enable adaptation to a large number of environmental conditions.

Citation Format: Luke Gilbert, Ben Herken. Environmental challenge rewires functional connections among human genes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA021.
Abstract PR002: Nimbolide targets RNF114 to induce the trapping of PARP1 and synthetic lethality in BRCA-mutated cancer
Authors: Li Peng , Zhen Yuanli , Kim Chiho , Liu Zhengshuai , Hao Jianwei , Deng Heping , Deng Hejun , Zhou Min , Wang Xu-Dong , Qin Tian , Yu Yonghao
Published: June 2024

Despite the tremendous success of PARP1 inhibitors (PARPi) for the treatment of BRCA mut tumors, intrinsic and acquired resistance to PARPi remains a critical challenge in the clinic. This is, at least in part, due to the incomplete understanding of the mechanism of action (MoA) of PARPi. Recent studies from both our lab and others have pointed to PARP1 trapping as a key determinant of the anticancer effects of PARP1 inhibitors (PARPi). However, the molecular underpinnings of PARP1 trapping are poorly understood. Here we performed a proteomics-based chromatin relocalization screen, and identified RNF114, as a PARylation-dependent, E3 ubiquitin ligase involved in DNA damage response. Upon sensing genotoxicity, RNF114 was recruited, in a PAR-dependent manner, to DNA lesions, where it targeted PARP1 for degradation. The blockade of this pathway interfered with the removal of PARP1 from DNA lesions, leading to profound PARP1 trapping. A unique feature of this pathway is its druggability. We showed that a natural product, nimbolide, inhibited the E3 ligase activity of RNF114 and thus caused PARP1 trapping. However, unlike conventional PARPi, nimbolide treatment induced the trapping of both PARP1 and PARylation-dependent DNA repair factors. The unique mechaism of action of nimbolide translated into its superior cytotoxicity against BRCA mut cancer cells, compared to regular PARPi. It is also able to potentially overcome intrinsic and acquired resistance to PARPi, both in vitro and in vivo. In collaboration with Dr. Tian Qin, we recently performed the first total synthesis of nimbolide via a pharmacophore-directed, late-stage coupling strategy. Using this method, we have obtained a large panel of novel nimbolide analogs with improved activity and drug-like properties. We have further garnered key SAR (structure-activity relationship) insights into nimbolide. These results point to the exciting possibility of translating nimbolide analogs into novel PARP1-targeting agents for the treatment of BRCA mut cancers.

Citation Format: Peng Li, Yuanli Zhen, Chiho Kim, Zhengshuai Liu, Jianwei Hao, Heping Deng, Hejun Deng, Min Zhou, Xu-Dong Wang, Tian Qin, Yonghao Yu. Nimbolide targets RNF114 to induce the trapping of PARP1 and synthetic lethality in BRCA-mutated cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr PR002.
Abstract PR013: Detecting pairwise and higher-order antagonistic epistatic effects among somatic cancer genotypes to discover synthetic lethality
Authors: Alfaro-Murillo Jorge A. , Dasari Krishna , Townsend Jeffrey P.
Published: June 2024

The mutual exclusivity of somatic variants in cancer suggests that current somatic variants can exert antagonistic epistatic effects on the selection of new mutations, contributing to a complex landscape of evolutionary trajectories. However, quantifying pairwise and higher-order epistatic effects—which are essential to estimation of the trajectory of likely cancer genotypes—has been a challenge. We have developed a continuous-time Markov chain model that enables the estimation of mutation origination and fixation, dependent on somatic cancer genotype. We coupled the continuous-time Markov chain model with an approach that deconvolutes the underlying mutation rates and selection intensities across trajectories of oncogenesis. By elucidating the routes of variant evolution and the strengths of selective forces at play, our approach lays the groundwork for quantifying antagonistic epistatic effects of specific somatic genotypes. We applied our approach to report the variant mutation rates, selection intensities, and consequent substitution rates for lung adenocarcinoma, comparing smoker and nonsmoker tumor cohorts. We describe the distinct influences of smoking on underlying mutation rates and on physiology affecting the selective regime of lung tissue. Inference of the most likely routes of site-specific variant evolution, as well as estimation of the selection strength operating on each step along the route represents a key component for prioritization, development, and implementation of personalized cancer therapies that target synthetic lethality.

Citation Format: Jorge A. Alfaro-Murillo, Krishna Dasari, Jeffrey P. Townsend. Detecting pairwise and higher-order antagonistic epistatic effects among somatic cancer genotypes to discover synthetic lethality [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr PR013.
FIGURE 3 from Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis
Authors: Rashidi Armin , Ebadi Maryam , Rehman Tauseef U. , Elhusseini Heba , Kazadi David , Halaweish Hossam , Khan Mohammad H. , Hoeschen Andrea , Cao Qing , Luo Xianghua , Kabage Amanda J. , Lopez Sharon , Ramamoorthy Sivapriya , Holtan Shernan G. , Weisdorf Daniel J. , Khoruts Alexander , Staley Christopher
Published: June 2024

Faecalibacterium and aGVHD risk. A, log-ratio lasso regression to find early post-FMT/placebo, genus-level, gut microbiota predictors of grade II–IV aGVHD. The y axis shows taxa in the final model. The probability for each taxon of being selected in the final model is shown along the x-axis. This probability is calculated from 100 4-fold cross-validated runs. Positive/negative signs show positive/negative associations, and the value (indicated by a color gradient) represents the strength of association. B, Comparison between early post-FMT versus early post-placebo samples in Faecalibacterium abundance. C, Comparison between the groups developing versus not developing grade II–IV aGVHD in early post-FMT/placebo Faecalibacterium abundance. D,Faecalibacterium abundance at pre-FMT/placebo and early post-FMT/placebo timepoints. Samples from the same patient are connected, with line type indicating randomized treatment arm and line color showing future grade II–IV aGVHD status. E,Faecalibacterium abundance in FMT donor samples and patient samples according to treatment arm and timepoint. F, Relationship between Faecalibacterium abundance change (pre- to post-FMT) and ASV-level binary similarity of early post-FMT versus donor composition of this genus. The gray shaded area shows the 95% confidence interval. Higher post-FMT Faecalibacterium abundance was strongly associated with a greater similarity between post-FMT sample and donor composition in Faecalibacterium ASVs (a simple measure of engraftment). G,Faecalibacterium change from pre-FMT to early post-FMT timepoints per FMT donor. Each box in B, C, and G shows the median (horizontal middle line) and interquartile range. Whisker lines indicate nonoutlier maximum and minimum values. A small jitter is included for better visualization. P values in B and C are from a Wilcoxon test and in G from a Kruskal–Wallis test. aGVHD: acute graft-versus-host disease; FMT: fecal microbiota transplantation.
Preditores de síndrome da apneia obstrutiva do sono em caminhoneiros
Authors: Medeiros Clarissa Mari de , Nakashima Erika , Feijó Esmeralda , Bonnet Fabianne , Silva Luana Sarti e , Gandra Lyvia Lorena
Published: June 2024

Traffic accidents are one of the leading causes of worldwide morbidity and mortality. Studies show that about 20% of these accidents are due to the lack of attention and/or excessive sleepiness. Drowsiness can be considered a potential indicator of Obstructive Sleep Apnea Syndrome (OSAS) when combined with overweight or obesity, high blood pressure and enlarged Cervical Circumference (CC). Studies suggest that professional drivers have a higher prevalence of OSAS than the general population, which is a matter of concern for traffic safety. Nevertheless, only in a few European countries is the subject of OSAS included as part of drivers’ license regulation criteria. In Brazil, Resolution 425 of 11.27.2012 specifically refers to the evaluation of sleep disorders, including its parameters. Since 2006, a project was initiated called the “Highway Health Command” (HHC), that consists of educational blitzes with spot surveys on Brazilian roads, in order to detect risk factors in truck drivers’ health. Thus, during the HHC held in two cities of São Paulo in 2014, data obtained from examinations and questionnaires were used for this observational and cross-sectional study, aiming to estimate the prevalence of OSAS predictors in truck drivers in São Paulo state (Brazil). Results showed that the indicators fell short of the desirable standards. High blood pressure showed deviations in more than ¼ drivers; body mass index greater than 30kg/ m² was noticed in 29.5% participants; CC was larger than 45cm in 6% drivers and 5.7% participants scored 12 or more at Epworth Sleepiness Scale (ESS). This study forewarns of the severity of drowsiness in national highways, emphasizing the need for progressive inclusion of this disease among medical conditions to which specific attention should be given in examinations of traffic medicine and drivers’ health.
O exame de corpo de delito ad cautelam
Authors: Zerbini Talita , Zerbini Tatiana , Cintra Raquel Barbosa
Published: June 2024

O crime de lesão corporal é previsto no Capítulo II do Título I da Parte Especial do Código Penal (CP) promulgado em 1940, estando descrito no caput do artigo 129 como “ofender a integridade corporal ou a saúde de outrem”. O presente trabalho visa esclarecer, sob ponto de vista jurídico e médico-legal, os parâmetros a serem utilizados para a realização do exame de corpo de delito ad cautelam. Um dos instrumentos utilizados para a garantia da integridade física e moral do preso é o exame de corpo de delito cautelar, ou seja, o exame médico-legal realizado no indivíduo sob custódia do Estado. Caso seja constatada lesão corporal, a classificação a ser utilizada é a mesma prevista no artigo 129 do CP. Além disso, o médico legista deve ficar atento a qualquer indício de prática de tortura.
The position of visual word forms in the anatomical and
representational space of visual categories in occipitotemporal
cortex
Authors: Pillet Ineke , Cerrahoğlu Begüm , Philips Roxane Victoria , Dumoulin Serge , de Beeck Hans Op
Published: June 2024

Recent reviews emphasized the need for investigating the complexity of multiple subareas of word selectivity and how this relates to selectivity for other visual categories, at the individual level at a high spatial resolution (without normalization or smoothing). To investigate this, both on the brain surface and in the representational space of the occipitotemporal cortex, we presented 19 participants with images of 20 different categories during 7T fMRI. These categories included several word-like conditions, and in addition cover many of the dimensions that have been suggested to define object space, such as animacy and real-world size. In the left hemisphere, we found three subareas of the visual word form area (VWFA) and one extra subarea around the pFus face-selective area. We also observed several areas of selectivity to hands that could consistently guide the localization of word and face areas. No clear predictive anatomical landmarks were found. Results of the right hemisphere were less clear, in part due to weaker word selectivity. In the representational space, word selectivity stood out from other categories. It had multiple neighboring categories at a similar distance (e.g., faces, bodies, hands, cars), so no special relationship was found with, for example, faces. These results enable a consistent and reliable way to locate subareas of word selectivity and may inspire future research into words in the representational space of the occipitotemporal cortex.
Scheler on the Concept of Productive Imagination in His Phenomenology and Metaphysics
Authors: Kelly Eugene
Published: June 2024

The paper is a critical analysis of Max Scheler’s concept of productive phantasy as it functions in two ways that the author finds philosophically interesting. First, it examines critically Scheler’s attempt to overturn the basis for the claims of David Hume that there is no genuine productive phantasy, and that all phantasy is reproductive where it is at all legitimate. Scheler responds with a theory of perception through which he attempts to demonstrate that productive phantasy is an essential component of all perceptual acts. Second, it examines Scheler’s development of the theory of productive phantasy in his late efforts in metaphysics and aesthetics. Here he claims that productive phantasy functions in the Ground of Being in the process of world-creation, with humankind as its helpmate. The result is a genetic phenomenology exhibiting the ways in which the mind comes to constitute a coherent world. The author agrees with Scheler that productive phantasy is indeed essential for the constitution of the everyday world and for the works of art that illuminate that world, but contrary to Scheler, the author argues that Scheler’s claims about the function of the term are incoherent, and it therefore cannot serve as one of the foundations of his “possibly true” metaphysical system.
Using Constitutional Imaginaries in Constitutional Comparison – yes, but how?
Authors: Teutsch Alexander
Published: June 2024

This article1 explores how constitutional imaginaries could be used in comparative constitutional research. It claims that, while western imaginaries are partly responsible for a western-oriented focus in constitutional comparison, constitutional imaginaries could, if conceptualised differently, fruitfully contribute to inquiries concerning different parts of the globe. Given this Janus-faced feature of constitutional imaginaries, the analysis highlights the variety of these imaginaries and their non-reducibility to a single overarching Imaginary. Building on Paul Blokker’s “Imaginary components”, making up two distinct ideal type Imaginaries, modernist and democratic, the article introduces a framework entailing three different normative stances in conceptualising imaginaries, being homogeneity, tension and disengaged coexistence. These stances range from a western-centred to a global-pluralistic take on Imaginaries. The benefits comparative constitutional research may obtain using this framework are twofold: first, it allows a more nuanced description of specific Imaginaries; second, it creates an adequate methodological setting to be applied also to non-western settings.
Gall wasp (Cynipoidea: Cynipidae and Diplolepididae) fauna of the Eastern Black Sea Region (Türkiye)
Authors: TATAROĞLU MUSA , KATILMIŞ YUSUF
Published: June 2024

In the period between October 2017 and September 2019, field studies were conducted with the aim of elucidating the gall wasp (Hymenoptera: Cynipidae and Diplolepididae) fauna of the Eastern Black Sea Region (Northeastern Türkiye). Gall samples were collected from 695 different localities within the research area, comprising a total of seven provinces (Artvin, Bayburt, Giresun, Gümüşhane, Ordu, Rize and Trabzon). As a result of these investigations, a total of 90 species belonging to 18 genera were recorded. Three of these species (Synergus consobrinus Giraud in Houard, 1911; S. reinhardi Mayr, 1872; S. ruficornis Hartig, 1840) represent new records for the inquiline (Synergini) fauna of Türkiye. The host plants, distributions, and distribution maps for all of the species recorded from the Eastern Black Sea Region are provided.
Genomic analysis based on chromosome-level genome assembly reveals Myrtaceae evolution and terpene biosynthesis of rose myrtle
Authors: Yang Ling , Jin Jingjing , Lyu Shanwu , Zhang Fangqiu , Cao Peijian , Qin Qiaomei , Zhang Guanghui , Feng Chen , Lu Peng , Li Huiguang , Deng Shulin
Published: June 2024

Background

Rose myrtle (Rhodomyrtus tomentosa (Ait.) Hassk), is an evergreen shrub species belonging to the family Myrtaceae, which is enriched with bioactive volatiles (α-pinene and β-caryophyllene) with medicinal and industrial applications. However, the mechanism underlying the volatile accumulation in the rose myrtle is still unclear.

Results

Here, we present a chromosome-level genomic assembly of rose myrtle (genome size = 466 Mb, scaffold N50 = 43.7 Mb) with 35,554 protein-coding genes predicted. Through comparative genomic analysis, we found that gene expansion and duplication had a potential contribution to the accumulation of volatile substances. We proposed that the action of positive selection was significantly involved in volatile accumulation. We identified 43 TPS genes in R. tomentosa. Further transcriptomic and TPS gene family analyses demonstrated that the distinct gene subgroups of TPS may contribute greatly to the biosynthesis and accumulation of different volatiles in the Myrtle family of shrubs and trees. The results suggested that the diversity of TPS-a subgroups led to the accumulation of special sesquiterpenes in different plants of the Myrtaceae family.

Conclusions

The high quality chromosome-level rose myrtle genome and the comparative analysis of TPS gene family open new avenues for obtaining a higher commercial value of essential oils in medical plants.
Allelopathic effect of the methanol extract of the weed species-red sorrel (Rumex acetosella L.) on the growth, phytohormone content and antioxidant activity of the cover crop - white clover (Trifolium repens L.)
Authors: Gam Ho-Jun , Injamum-Ul-Hoque Md. , Kang Yosep , Ahsan S. M. , Hasan Md. Mahadi , Shaffique Shifa , Kang Sang-Mo , Lee In-Jung
Published: June 2024

Allelopathy is a biological process in which one organism releases biochemicals that affect the growth and development of other organisms. The current investigation sought to determine the allelopathic effect of Rumex acetosella on white clover (Trifolium repens) growth and development by using its shoot extract (lower IC50 value) as a foliar treatment. Here, different concentrations (25, 50, 100, and 200 g/L) of shoot extract from Rumex acetosella were used as treatments. With increasing concentrations of shoot extract, the plant growth parameters, chlorophyll and total protein content of Trifolium repens decreased. On the other hand, ROS, such as O2.− and H2O2, and antioxidant enzymes, including SOD, CAT, and POD, increased with increasing shoot extract concentration. A phytohormonal study indicated that increased treatment concentrations increased ABA and SA levels while JA levels were reduced. For the identification of allelochemicals, liquid‒liquid extraction, thin-layer chromatography, and open-column chromatography were conducted using R. acetosella shoot extracts, followed by a seed bioassay on the separated layer. A lower IC50 value was obtained through GC/MS analysis. gammaSitosterol was identified as the most abundant component. The shoot extract of Rumex acetosella has strong allelochemical properties that may significantly impede the growth and development of Trifolium repens. This approach could help to understand the competitive abilities of this weed species and in further research provide an alternate weed management strategy.
Maternal serum biomarkers of placental insufficiency at 24–28 weeks of pregnancy in relation to the risk of delivering small-for-gestational-age infant in Sylhet, Bangladesh: a prospective cohort study
Authors: Rahman Sayedur , Islam Md. Shafiqul , Roy Anjan Kumar , Hasan Tarik , Chowdhury Nabidul Haque , Ahmed Salahuddin , Raqib Rubhana , Baqui Abdullah H. , Khanam Rasheda
Published: June 2024

Background

Small-for-gestational-age (SGA), commonly caused by poor placentation, is a major contributor to global perinatal mortality and morbidity. Maternal serum levels of placental protein and angiogenic factors are changed in SGA. Using data from a population-based pregnancy cohort, we estimated the relationships between levels of second-trimester pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF), and serum soluble fms-like tyrosine kinase-1 (sFlt-1) with SGA.

Methods

Three thousand pregnant women were enrolled. Trained health workers prospectively collected data at home visits. Maternal blood samples were collected, serum aliquots were prepared and stored at -80℃. Included in the analysis were 1,718 women who delivered a singleton live birth baby and provided a blood sample at 24–28 weeks of gestation. We used Mann-Whitney U test to examine differences of the median biomarker concentrations between SGA (< 10th centile birthweight for gestational age) and appropriate-for-gestational-age (AGA). We created biomarker concentration quartiles and estimated the risk ratios (RRs) and 95% confidence intervals (CIs) for SGA by quartiles separately for each biomarker. A modified Poisson regression was used to determine the association of the placental biomarkers with SGA, adjusting for potential confounders.

Results

The median PlGF level was lower in SGA pregnancies (934 pg/mL, IQR 613–1411 pg/mL) than in the AGA (1050 pg/mL, IQR 679–1642 pg/mL; p < 0.001). The median sFlt-1/PlGF ratio was higher in SGA pregnancies (2.00, IQR 1.18–3.24) compared to AGA pregnancies (1.77, IQR 1.06–2.90; p = 0.006). In multivariate regression analysis, women in the lowest quartile of PAPP-A showed 25% higher risk of SGA (95% CI 1.09–1.44; p = 0.002). For PlGF, SGA risk was higher in women in the lowest (aRR 1.40, 95% CI 1.21–1.62; p < 0.001) and 2nd quartiles (aRR 1.30, 95% CI 1.12–1.51; p = 0.001). Women in the highest and 3rd quartiles of sFlt-1 were at reduced risk of SGA delivery (aRR 0.80, 95% CI 0.70–0.92; p = 0.002, and aRR 0.86, 95% CI 0.75–0.98; p = 0.028, respectively). Women in the highest quartile of sFlt-1/PlGF ratio showed 18% higher risk of SGA delivery (95% CI 1.02–1.36; p = 0.025).

Conclusions

This study provides evidence that PAPP-A, PlGF, and sFlt-1/PlGF ratio measurements may be useful second-trimester biomarkers for SGA.
Network development in workplace health promotion – empirically based insights from a cross-company network promoting physical activity in Germany
Authors: Gernert Madeleine , Fohr Gabriele , Schaller Andrea
Published: June 2024

Background

In the field of health promotion, interorganisational networks are of growing relevance. However, systematic and target-oriented network management is of utmost importance for network development. The aim of this article is to report on the development of a cross-company network promoting physical activity, and to identify necessary activities and competencies for a systematic network management.

Methods

The network was systematically planned and implemented in a German technology park comprising different companies. To assess and describe the development of the network, quantitative social network analysis was conducted. To answer the question on the activities and competencies for systematic network development semi-structured interviews with participating stakeholders, and a focus group discussion with health promotion experts were conducted. The interviews were analysed deductively and inductively with the structuring content analysis method and the focus group discussion was analysed deductively by summarising key aspects of the discussion.

Results

Network metrics showed that the network became larger and denser during the planning phase, and stagnated during the implementation phase. As key facilitators for network development, participation of all stakeholders, a kick-off event, and the driving role of a network manager were identified. Necessary activities of the network manager were related to structural organisation, workplace health promotion offers, and cross-sectional tasks. The results suggested that not only professional and methodological competencies, but also social and self-competencies were required by the manager.

Conclusions

Our study provides initial guidance regarding the activities and required competencies of an interorganisational network manager. The results are of particular relevance for the context of workplace health promotion, since a network manager can be considered as a driving role for planning and implementing a cross-company network.

Trial registration

The study is registered in the German Clinical Trials Register (DRKS00020956, 18/06/2020).
The identification of hub genes associated with pure ground glass nodules using weighted gene co-expression network analysis
Authors: Cheng Yuan , Song Zuoqing
Published: June 2024

Background

Whether there are invasive components in pure ground glass nodules(pGGNs) in the lungs is still a huge challenge to forecast. The objective of our study is to investigate and identify the potential biomarker genes for pure ground glass nodule(pGGN) based on the method of bioinformatics analysis.

Methods

To investigate differentially expressed genes (DEGs), firstly the data obtained from the gene expression omnibus (GEO) database was used.Next Weighted gene co-expression network analysis (WGCNA) investigate the co-expression network of DEGs. The black key module was chosen as the key one in correlation with pGGN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were done. Then STRING was uesd to create a protein-protein interaction (PPI) network, and the chosen module genes were analyzed by Cytoscape software.In addition the polymerase chain reaction (PCR) was used to evaluate the value of these hub genes in pGGN patients’ tumor tissues compared to controls.

Results

A total of 4475 DEGs were screened out from GSE193725, then 225 DEGs were identified in black key module, which were found to be enriched for various functions and pathways, such as extracellular exosome, vesicle, ribosome and so on. Among these DEGs, 6 overlapped hub genes with high degrees of stress method were selected. These hub genes include RPL4, RPL8, RPLP0, RPS16, RPS2 and CCT3.At last relative expression levels of CCT3 and RPL8 mRNA were both regulated in pGGN patients’ tumor tissues compared to controls.

Conclusions

To summarize, the determined DEGs, pathways, modules, and overlapped hub genes can throw light on the potential molecular mechanisms of pGGN.
Naming racism as a root cause of inequities in palliative care research: a scoping review
Authors: Algu Kavita , Wales Joshua , Anderson Michael , Omilabu Mariam , Briggs Thandi , Kurahashi Allison M.
Published: June 2024

Background

Racial and ethnic inequities in palliative care are well-established. The way researchers design and interpret studies investigating race- and ethnicity-based disparities has future implications on the interventions aimed to reduce these inequities. If racism is not discussed when contextualizing findings, it is less likely to be addressed and inequities will persist.

Objective

To summarize the characteristics of 12 years of academic literature that investigates race- or ethnicity-based disparities in palliative care access, outcomes and experiences, and determine the extent to which racism is discussed when interpreting findings.

Methods

Following Arksey & O’Malley’s methodology for scoping reviews, we searched bibliographic databases for primary, peer reviewed studies globally, in all languages, that collected race or ethnicity variables in a palliative care context (January 1, 2011 to October 17, 2023). We recorded study characteristics and categorized citations based on their research focus—whether race or ethnicity were examined as a major focus (analyzed as a primary independent variable or population of interest) or minor focus (analyzed as a secondary variable) of the research purpose, and the interpretation of findings—whether authors directly or indirectly discussed racism when contextualizing the study results.

Results

We identified 3000 citations and included 181 in our review. Of these, most were from the United States (88.95%) and examined race or ethnicity as a major focus (71.27%). When interpreting findings, authors directly named racism in 7.18% of publications. They were more likely to use words closely associated with racism (20.44%) or describe systemic or individual factors (41.44%). Racism was directly named in 33.33% of articles published since 2021 versus 3.92% in the 10 years prior, suggesting it is becoming more common.

Conclusion

While the focus on race and ethnicity in palliative care research is increasing, there is room for improvement when acknowledging systemic factors – including racism – during data analysis. Researchers must be purposeful when investigating race and ethnicity, and identify how racism shapes palliative care access, outcomes and experiences of racially and ethnically minoritized patients.
Quality of palliative and end-of-life care: a qualitative study of experts’ recommendations to improve indicators in Quebec (Canada)
Authors: Allard Emilie , Dumaine Sarah , Sasseville Martin , Gabet Morgane , Duhoux Arnaud
Published: June 2024

Background

In 2021, the National Institute of Public Health (INSPQ) (Quebec, Canada), published an update of the palliative and end-of-life care (PEoLC) indicators. Using these updated indicators, this qualitative study aimed to explore the point of view of PEoLC experts on how to improve access and quality of care as well as policies surrounding end-of-life care.

Methods

Semi-directed interviews were conducted with palliative care and policy experts, who were asked to share their interpretations on the updated indicators and their recommendations to improve PEoLC. A thematic analysis method was used.

Results

The results highlight two categories of interpretations and recommendations pertaining to: (1) data and indicators and (2) clinical and organizational practice. Participants highlight the lack of reliability and quality of the data and indicators used by political and clinical stakeholders in evaluating PEoLC. To improve data and indicators, they recommend: improving the rigour and quality of collected data, assessing death percentages in all healthcare settings, promoting research on quality of care, comparing data to EOL care directives, assessing use of services in EOL, and creating an observatory on PEoLC. Participants also identified barriers and disparities in accessing PEoLC as well as inconsistency in quality of care. To improve PEoLC, they recommend: early identification of palliative care patients, improving training for all healthcare professionals, optimizing professional practice, integrating interdisciplinary teams, and developing awareness on access disparities.

Conclusions

Results show that PEoLC is an important aspect of public health. Recommendations issued are relevant to improve PEoLC in and outside Quebec.
Exploring the mechanism of fraxetin against acute myeloid leukemia through cell experiments and network pharmacology
Authors: Fang Tingting , Liu Lanqin , Liu Wenjun
Published: June 2024

Objective

Previous studies have shown that fraxetin has antitumor activity in a variety of tumors, but its role in acute myeloid leukemia (AML) remains unclear. In this study, we aimed to evaluate the anti-AML effect of fraxetin through cell experiments and network pharmacology analysis.

Methods

The inhibitory and apoptotic effects of fraxetin on AML cells were determined by CCK-8 and flow cytometry experiments. Potential targets of fraxetin and AML-related targets were screened using public databases. PPI network, GO functional enrichment and KEGG pathway enrichment analyses were performed to predict the hub targets and signaling pathways by which fraxetin alleviates AML. Molecular docking was used to determine the fraxetin binding sites on hub targets. Using the GEPIA database, the expression of hub targets was analyzed in relation to the overall survival of AML patients.

Results

Cell experiments showed that fraxetin inhibits AML cell proliferation and induces apoptosis. To explore the potential mechanism of fraxetin, 29 shared targets of fraxetin and AML were obtained through screening online public databases. Among them, AKT1, TNF, SRC, etc., are related to AML cell apoptosis. The expression levels of SRC, NOS3, VAV1, LYN, and PTGS1 were associated with the overall survival of AML patients (p value < 0.05). The enrichment analysis results identified the main pathways, namely, focal adhesion and the PI3K-AKT signaling pathway, that affected the proliferation and apoptosis of AML cells. The analysis of hub targets of the PPI network showed that AKT1, TNF, CTNNB1, etc., were hub targets, which were related to the proliferation and apoptosis of AML cells. The results of molecular docking showed that the hub targets had good binding with fraxetin.

Conclusion

Fraxetin may inhibit AML cell proliferation and induce AML cell apoptosis through multiple targets, such as AKT1, SRC, and EGFR, and multiple pathways, such as focal adhesion and the PI3K-AKT signaling pathway.
Community readiness and acceptance for the implementation of a novel malaria vaccine among at-risk children in sub-saharan Africa: a systematic review protocol
Authors: Kigongo Eustes , Kabunga Amir , Opollo Marc Sam , Tumwesigye Raymond , Musinguzi Marvin , Akello Anne Ruth , Nabaziwa Jannat , Hardido Temesgen Geta , Puleh Sean Steven
Published: June 2024

Background

The World Health Organization novel malaria vaccine for at-risk children has the potential to greatly reduce the current malaria burden in sub-Saharan Africa. However, most studies have reported contradictory findings regarding community willingness for the vaccine, which could easily undermine the expected benefits of the vaccine. This study aims to ascertain the current state of community readiness and acceptance for the implementation of a novel malaria vaccine (RTS,S/ASO1) among at-risk children in sub-Saharan Africa, based on available evidence.

Methods

This study will follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol (PRISMA-P) guidelines. Relevant studies will be comprehensively searched from PubMed, ScienceDirect, Web of Science, Google Scholar, and African journals online, in accordance with the Cochrane search guidelines. Two independent reviewers will screen titles, abstracts and full texts of eligible studies based on some specified eligibility criteria. When it is feasible to conduct a meta-analysis, a random effects model will be employed to estimate the common effect due to anticipated high heterogeneity of the data. The effect measure for readiness or acceptance will be reported as a pooled proportion with corresponding 95% confidence interval. Additionally, odds ratios with 95% confidence interval will be estimated to assess factors associated with readiness. These will be presented on a forest plot.

Dissemination plans

The findings of the study will be peer-reviewed and published in a scientific journal. Conference presentations will also be made to the different stakeholders in the malaria vaccination campaigns.

Systematic review registration

The protocol has been registered with PROSPERO Registration Number: CRD42023480528.
Chloroquine has shown high therapeutic efficacy against uncomplicated Plasmodium vivax malaria in southern Ethiopia: seven decades after its introduction
Authors: Mare Anteneh Kassahun , Mohammed Hussein , Sime Heven , Hailgiorgis Henok , Gubae Kale , Gidey Bekuretsion , Haile Mebrahtom , Assefa Gudissa , Bekele Worku , Auburn Sarah , Price Rick , Parr Jonathan B. , Juliano Jonathan J. , Tasew Geremew , Abay Solomon Mequanente , Assefa Ashenafi
Published: June 2024

Background

Plasmodium vivax malaria is a leading cause of morbidity in Ethiopia. The first-line treatment for P. vivax is chloroquine (CQ) and primaquine (PQ), but there have been local reports of CQ resistance. A clinical study was conducted to determine the efficacy of CQ for the treatment of P. vivax malaria in southern Ethiopia.

Methods

In 2021, patients with P. vivax mono-infection and uncomplicated malaria were enrolled and treated with 25 mg/kg CQ for 3 consecutive days. Patients were followed for 28 days according to WHO guidelines. The data were analysed using per-protocol (PP) and Kaplan‒Meier (K‒M) analyses to estimate the risk of recurrent P. vivax parasitaemia on day 28.

Results

A total of 88 patients were enrolled, 78 (88.6%) of whom completed the 28 days of follow-up. Overall, 76 (97.4%) patients had adequate clinical and parasitological responses, and two patients had late parasitological failures. The initial therapeutic response was rapid, with 100% clearance of asexual parasitaemia within 48 h.

Conclusion

Despite previous reports of declining chloroquine efficacy against P. vivax, CQ retains high therapeutic efficacy in southern Ethiopia, supporting the current national treatment guidelines. Ongoing clinical monitoring of CQ efficacy supported by advanced molecular methods is warranted to inform national surveillance and ensure optimal treatment guidelines.
Magnetogenetics as a promising tool for controlling cellular signaling pathways
Authors: Latypova Anastasiia A. , Yaremenko Alexey V. , Pechnikova Nadezhda A. , Minin Artem S. , Zubarev Ilya V.
Published: June 2024

Magnetogenetics emerges as a transformative approach for modulating cellular signaling pathways through the strategic application of magnetic fields and nanoparticles. This technique leverages the unique properties of magnetic nanoparticles (MNPs) to induce mechanical or thermal stimuli within cells, facilitating the activation of mechano- and thermosensitive proteins without the need for traditional ligand-receptor interactions. Unlike traditional modalities that often require invasive interventions and lack precision in targeting specific cellular functions, magnetogenetics offers a non-invasive alternative with the capacity for deep tissue penetration and the potential for targeting a broad spectrum of cellular processes. This review underscores magnetogenetics’ broad applicability, from steering stem cell differentiation to manipulating neuronal activity and immune responses, highlighting its potential in regenerative medicine, neuroscience, and cancer therapy. Furthermore, the review explores the challenges and future directions of magnetogenetics, including the development of genetically programmed magnetic nanoparticles and the integration of magnetic field-sensitive cells for in vivo applications. Magnetogenetics stands at the forefront of cellular manipulation technologies, offering novel insights into cellular signaling and opening new avenues for therapeutic interventions.
A thorough analysis of data on the correlation between COL9A1 polymorphisms and the susceptibility to congenital talipes equinovarus: a meta-analysis
Authors: Golshan-Tafti Mohammad , Dastgheib Seyed Alireza , Alijanpour Kamran , Bahrami Reza , Mazaheri Mahta , Neamatzadeh Hossein
Published: June 2024

Background

Congenital talipes equinovarus (CTEV) is a prevalent pediatric deformity with a multifactorial etiology. The objective of this meta-analysis was to explore the association between genetic variations in COL9A1 and the susceptibility to CTEV.

Methods

A comprehensive analysis of pertinent literature released before November 15, 2023, in electronic bibliographic databases was carried out. The importance of the connection was clarified through odds ratios (ORs) with 95% confidence intervals (CIs), utilizing random or fixed-effects models depending on study heterogeneity. Statistical analysis was executed using Comprehensive Meta-Analysis software (Version 4.0).

Results

A total of eight case-control studies involving 833 CTEV patients and 1280 healthy individuals were included in the analysis. Among these, four studies investigated the rs1135056 variant, encompassing 432 CTEV cases and 603 controls; two studies examined the rs35470562 variant, with 189 CTEV cases and 378 controls; and two studies explored the rs592121 variant, including 212 CTEV cases and 299 controls. The results revealed a significant association between the rs1135056 and rs35470562 polymorphisms in the COL9A1 gene, suggesting an increased risk of CTEV in the overall population. Conversely, no such association was found for the rs592121 variant.

Conclusion

Our findings reveal a substantial association between the genetic variants COL9A1 rs1135056 and rs35470562 and susceptibility to CTEV. Conversely, the variant rs592121 did not exhibit any corresponding link. However, the limitations imposed by the small study population have compromised the statistical reliability and generalizability of the results.
Aspartate-β-hydroxylase and hypoxia marker expression in head and neck carcinomas: implications for HPV-associated tumors
Authors: Smahelova Jana , Pokryvkova Barbora , Stovickova Eliska , Grega Marek , Vencalek Ondrej , Smahel Michal , Koucky Vladimir , Malerova Simona , Klozar Jan , Tachezy Ruth
Published: June 2024

Background

A proportion of head and neck carcinomas (HNSCCs) are induced by high-risk human papillomaviruses (HPVs) and are associated with better patient outcomes compared to patients with HNSCCs related to tobacco and alcohol abuse. In the microenvironment of solid tumors, including HNSCCs, oxygen levels are often reduced, and a hypoxic state is induced. This can lead to a poor treatment response and a worse patient prognosis. One of the hypoxia-responsive genes is aspartate-β-hydroxylase (ASPH), whose activity promotes the growth, invasiveness, and metastasis of many types of solid tumors.

Methods

In our study, HNSCC samples were analyzed for the expression of ASPH and selected endogenous hypoxia markers by real-time PCR and/or multiplex fluorescence immunohistochemistry.

Results

Except for the EPAS1 gene, which had higher mRNA expression in the HPV-negative group of HNSCC (p < 0.05), we found no other differences in the expression of the tested genes that were related to HPV status. On the contrary, a statistically significantly higher number of cells producing ASPH (p < 0.0001), HIF1A (p < 0.0001), GLUT1 (p < 0.0001), and MMP13 (p < 0.05) proteins were detected in the HPV-positive tumor group than in the HPV-negative sample group. All the evaluated markers, except for MMP9/13, were more abundant in the tumor parenchyma than in the tumor stroma. The Cox proportional hazard models showed that increased numbers of cells with GLUT1 and HIF1A protein expression were positive prognostic markers for overall and disease-specific survival in patients independent of HPV tumor status.

Conclusion

The study examined HNSCC samples and found that elevated ASPH and hypoxia marker proteins, typically associated with poor prognosis, may actually indicate active HPV infection, the strongest prognostic factor in HNSCC patients. In cases where HPV status is uncertain, increased expression of HIF1A and GLUT1 can serve as positive prognostic factors.
112 What’s your emergency? Overview of mental health and sleep disorders among emergency medical dispatchers in a French 112 call center
Authors: Giaume Louise , Daniel Y. , Jimenez A. , Burlaton G. , Jost D. , Petitclerc M. , Briche F. , Hertgen P. , Amzstut P. , Mercier P. , Louyot C. , Trousselard M. , Travers S.
Published: June 2024

Background

Emergency medical dispatchers (EMD) experience significant occupational stress. Medical dispatching includes call-taking, triage, dispatch, and providing callers gesture guidance to the victims. Every decision has a major impact on the patient’s outcome. Chronic exposure to stress and potentially traumatic situations, combined with night shifts can impact the stress response and physical health of staff.

Objectives

To evaluate the prevalence of mental health and sleep disorders among EMD personnel working in a 112-call center, prior to an evidence-based prevention intervention (primary outcome); and to assess the relationship between health outcomes and DM (secondary outcome).

Methods

We conducted a descriptive, monocentric study with 109 EMD. HAD Anxiety (HAD-A) and Depression (HAD-D) scores, and the PTSD checklist for DSM-5 (PCL-5) were used to explore mental health disorders. The Epworth Sleepiness Scale, and other analog scales were used to explore sleep disorders. DM resources were assessed using the Freiburg Mindfulness Inventory (FMI), and its Presence and Acceptance subscales.

Results

A total of 72% of the EMD working in the call center were included. Of these, 16.6% had moderate anxiety disorder, and 6.4% had an anxiety disorder (Mean HAD-A: 6.05 ± 2.88). Furthermore, 16.6% had a moderate depression disorder, and 6.4% had a depression disorder (Mean HAD-D: 4.28 ± 3.28), and 16% had symptoms of PTSD (Mean PCL-5: 17.57 ± 13.67). Turning to sleep, 39% may suffer from excessive daytime sleepiness (EDS), and 10% had confirmed EDS (Mean Epworth score 10.47 ± 4.41). Finally, 39% had moderate insomnia, and 59% had severe insomnia (Mean insomnia: 13.84 ± 5.77.). Medium-strength negative correlations were found between mental health and DM (FMI scores and sub-scores: −0.48 < r < − 0.29; 0.001 < p < 0.004); and a positive correlation was found between DM and daytime awareness (0.22 < r < 0.26; 0.01 < p < 0.03).

Conclusion

The prevalence of depression, symptoms of PTSD, and sleep disorders in our sample of EMD is significant, and confirms findings reported in the literature. The EMD population may benefit from specific, multi-level interventions that target mindfulness, sleep, and ergonomics to improve their mental and physical health.