bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between environmental gradient of anthropization and phenotypic plasticity in two species of triatomines
Authors: Fiad Federico G. , Cardozo Miriam , Nattero Julieta , Gigena Gisel V. , Gorla David E. , Rodríguez Claudia S. 
Published: April 2024

Abstract
Background
Triatoma garciabesi and T. guasayana are considered secondary vectors of Trypanosoma cruzi and frequently invade rural houses in central Argentina. Wing and head structures determine the ability of triatomines to disperse. Environmental changes exert selective pressures on populations of both species, promoting changes in these structures that could have consequences for flight dispersal. The aim of this study was to investigate the relationship between a gradient of anthropization and phenotypic plasticity in flight-related traits.

Methods
The research was carried out in Cruz del Eje and Ischilín departments (Córdoba, Argentina) and included 423 individuals of the two species of triatomines. To measure the degree of anthropization, a thematic map was constructed using supervised classification, from which seven landscapes were selected, and nine landscape metrics were extracted and used in a hierarchical analysis. To determine the flight capacity and the invasion of dwellings at different levels of anthropization for both species, entomological indices were calculated. Digital images of the body, head and wings were used to measure linear and geometric morphometric variables related to flight dispersion. One-way ANOVA and canonical variate analysis (CVA) were used to analyze differences in size and shape between levels of anthropization. Procrustes variance of shape was calculated to analyze differences in phenotypic variation in heads and wings.

Results
Hierarchical analysis was used to classify the landscapes into three levels of anthropization: high, intermediate and low. The dispersal index for both species yielded similar results across the anthropization gradient. However, in less anthropized landscapes, the density index was higher for T. garciabesi. Additionally, in highly anthropized landscapes, females and males of both species exhibited reduced numbers. Regarding phenotypic changes, the size of body, head and wings of T. garciabesi captured in the most anthropized landscapes was greater than for those captured in less anthropized landscapes. No differences in body size were observed in T. guasayana collected in the different landscapes. However, males from highly anthropized landscapes had smaller heads and wings than those captured in less anthropized landscapes. Both wing and head shapes varied between less and more anthropogenic environments in both species.

Conclusions
Results of the study indicate that the flight-dispersal characteristics of T. garciabesi and T. guasayana changed in response to varying degrees of anthropization.

Graphical Abstract
Conserved methylation signatures associate with the tumor immune microenvironment and immunotherapy response
Authors: Qin Qingqing , Zhou Ying , Guo Jintao , Chen Qinwei , Tang Weiwei , Li Yuchen , You Jun , Li Qiyuan 
Published: April 2024

AbstractBackgroundAberrant DNA methylation is a major characteristic of cancer genomes. It remains unclear which biological processes determine epigenetic reprogramming and how these processes influence the variants in the cancer methylome, which can further impact cancer phenotypes.MethodsWe performed pairwise permutations of 381,900 loci in 569 paired DNA methylation profiles of cancer tissue and matched normal tissue from The Cancer Genome Atlas (TCGA) and defined conserved differentially methylated positions (DMPs) based on the resulting null distribution. Then, we derived independent methylation signatures from 2,465 cancer-only methylation profiles from the TCGA and 241 cell line-based methylation profiles from the Genomics of Drug Sensitivity in Cancer (GDSC) cohort using nonnegative matrix factorization (NMF). We correlated DNA methylation signatures with various clinical and biological features, including age, survival, cancer stage, tumor immune microenvironment factors, and immunotherapy response. We inferred the determinant genes of these methylation signatures by integrating genomic and transcriptomic data and evaluated the impact of these signatures on cancer phenotypes in independent bulk and single-cell RNA/methylome cohorts.ResultsWe identified 7,364 differentially methylated positions (2,969 Hyper-DMPs and 4,395 Hypo-DMPs) in nine cancer types from the TCGA. We subsequently retrieved three highly conserved, independent methylation signatures (Hyper-MS1, Hypo-MS1, and Hypo-MS4) from cancer tissues and cell lines based on these Hyper and Hypo-DMPs. Our data suggested that Hypo-MS4 activity predicts poor survival and is associated with immunotherapy response and distant tumor metastasis, and Hypo-MS4 activity is related to TP53 mutation and FOXA1 binding specificity. In addition, we demonstrated a correlation between the activities of Hypo-MS4 in cancer cells and the fractions of regulatory CD4 + T cells with the expression levels of immunological genes in the tumor immune microenvironment.ConclusionsOur findings demonstrated that the methylation signatures of distinct biological processes are associated with immune activity in the cancer microenvironment and predict immunotherapy response.
Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression
Authors: Chen Zegeng , Huang He , Hong Huangming , Huang Huageng , Weng Huawei , Yu Le , Xiao Jian , Wang Zhao , Fang Xiaojie , Yao Yuyi , Yue Jia-Xing , Lin Tongyu 
Published: April 2024

AbstractBackgroundNatural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored.MethodsHere, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels.ResultsOur study not only confirmed previously reported common NKTCL mutational targets likeSTAT3,TP53, andDDX3Xbut also unveiled several novel high-frequency mutational targets such asPRDM9,DST, andRBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0–C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole.ConclusionsThe striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.
Association between stress hyperglycemia ratio and diabetes mellitus mortality in American adults: a retrospective cohort study and predictive model establishment based on machine learning algorithms (NHANES 2009–2018)
Authors: Yan Fengjuan , Zhao Limin , Quan Xiaoqing , Zhu Jialiang 
Published: April 2024

Abstract
Background
Stress hyperglycemia is a physiological response of the body under stress to make adaptive adjustments in response to changes in the internal environment. The stress hyperglycemia ratio (SHR) is a new indicator after adjusting the basal blood glucose level of the population. Previous studies have shown that SHR is associated with poor prognosis in many diseases, such as cardiovascular and cerebrovascular diseases and delirium in elderly patients. However, there are currently no studies on the correlation between SHR and the general U.S. population. The purpose of this study was to examine the association between SHR and adverse outcomes among adults in the United States in general.

Methods
Data on 13,315 follow-up cohorts were extracted from NHANES. The study population was divided into four groups according to quartiles of SHR. The primary outcomes were all-cause mortality and diabetes mellitus mortality. The relationship between SHR and outcomes was explored using restricted cubic splines, COX proportional hazards regression, Kaplan-Meier curves, and mediation effects. SHR is incorporated into eight machine learning algorithms to establish a prediction model and verify the prediction performance.

Results
A total of 13,315 individual data were included in this study. Restricted cubic splines demonstrated a “U-shaped” association between SHR and all-cause mortality and diabetes mellitus mortality, indicating that increasing SHR is associated with an increased risk of adverse events. Compared with lower SHR, higher SHR was significantly associated with an increased risk of all cause mortality and diabetes mellitus mortality (HR > 1, P < 0.05). The mediating effect results showed that the positively mediated variables were segmented neutrophils and aspartate aminotransferase, and the negatively mediated variables were hemoglobin, red blood cell count, albumin, and alanine aminotransferase. The ROC of the eight machine learning algorithm models are XGBoost (0.8688), DT (0.8512), KNN (0.7966), RF (0.8417), Logistic regression (0.8633), ENET (0.8626), SVM (0.8327) and MLP (0.8662).

Conclusion
SHR can be used as a predictor of all cause mortality and diabetes mellitus mortality in the general adult population in the United States. Higher SHR is significantly associated with an increased risk of poor prognosis, especially in those aged < 65 years and in women.
Reference intervals of complete blood count parameters in the adult western Sudanese population
Authors: Mustafa Malak Ibrahim , Ali Ibrahim Abdelrhim , Mohammed Muaath Ahmed , Taha Elmutaz Hussien , Awad Kamal Mohamed , Musa Omer Abdelaziz 
Published: April 2024

Abstract
Background
A complete blood count (CBC) analysis is one of the most common conventional blood tests that physicians frequently prescribe.

The objective
of this study was to determine the reference intervals (RIs) of CBC parameters in the population of healthy adults living in the western Sudan region.

Methods
A cross-sectional study of healthy people residing in the western area of Sudan was carried out. We assessed the CBC RIs in samples taken from 153 individuals using an automated haematology analyser (Sysmex KX-21) and a modified Box–Cox transformation procedure to transform the data into a Gaussian distribution after eliminating outliers using the Dixon method. IBM SPSS Statistics version 25 was used to analyse the data, and t tests were employed to examine variations in the mean CBC parameters according to sex and age. P was considered significant at ≤ 0.05.

Results
Beyond all the other measured values, the only CBC parameters that significantly differed between the sexes were haemoglobin (HGB) and white blood cell (WBC) counts. Women were found to experience more WBC counts than men did. However, they have less HGB RIs.The male participants in our study exhibited lower WBC count RIs, a significantly lower limit, and a greater upper limit of platelet RIs than did the individuals from other nations.

Conclusions
Compared with males, females had higher platelet and WBC counts and lower HGB.
Delirium screening in the emergency department: evaluation and intervention
Authors: Meged-Book Tehilah , Frenkel Reut , Nikonov Anna , Zeldetz Vladimir , Kosto Amit , Schwarzfuchs Dan , Freud Tamar , Press Yan 
Published: April 2024

Abstract
Background
Between 8–17% of older adults, and up to 40% of those arriving from nursing homes, present with delirium upon admission to the Emergency Department (ED). However, this condition often remains undiagnosed by ED medical staff. We investigated the prevalence of delirium among patients aged 65 and older admitted to the ED and assessed the impact of a prospective study aimed at increasing awareness.

Methods
The study was structured into four phases: a "pre-intervention period" (T0); an "awareness period" (T1), during which information about delirium and its diagnosis was disseminated to ED staff; a "screening period" (T2), in which dedicated evaluators screened ED patients aged 65 and older; and a "post-intervention period" (T3), following the departure of the evaluators. Delirium screening was conducted using the Brief Confusion Assessment Method (bCAM) questionnaire.

Results
During the T0 and T1 periods, the rate of delirium diagnosed by ED staff was below 1%. The evaluators identified a delirium rate of 14.9% among the screened older adults during the T2 period, whereas the rate among those assessed by ED staff was between 1.6% and 1.9%. Following the evaluators' departure in the T3 period, the rate of delirium diagnosis decreased to 0.89%.

Conclusions
This study underscores that a significant majority of older adult delirium cases remain undetected by ED staff. Despite efforts to increase awareness, the rate of diagnosis did not significantly improve. While the presence of dedicated delirium evaluators slightly increased the diagnosis rate among patients assessed by ED staff, this rate reverted to pre-intervention levels after the evaluators left. These findings emphasize the necessity of implementing mandatory delirium screening during ED triage and throughout the patient’s stay.
Severe Legionnaires’ disease
Authors: Rello Jordi , Allam Camille , Ruiz-Spinelli Alfonsina , Jarraud Sophie 
Published: April 2024

Abstract
Background
Legionnaires’ disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and advances in molecular testing have improved the diagnosis. LD entails intensive care unit (ICU) admission in almost one-third of cases, and the mortality rate ranges from 4% to 40%. This review aims to discuss recent advances in the study of this condition and to provide an update on the diagnosis, pathogenesis and management of severe LD.

Results
The overall incidence of LD has increased worldwide in recent years due to the higher number of patients with risk factors, especially immunosuppression, and to improvements in diagnostic methods. Although LD is responsible for only around 5% of all-cause CAP, it is one of the three most common causes of CAP requiring ICU admission. Mortality in ICU patients, immunocompromised patients or patients with a nosocomial source of LD can reach 40% despite appropriate antimicrobial therapy. Regarding pathogenesis, no Legionella-specific virulence factors have been associated with severity; however, recent reports have found high pulmonary Legionella DNA loads, and impairments in immune response and lung microbiome in the most severe cases. The clinical picture includes severe lung injury requiring respiratory and/or hemodynamic support, extrapulmonary symptoms and non-specific laboratory findings. LD diagnostic methods have improved due to the broad use of UAT and the development of molecular methods allowing the detection of all Lp serogroups. Therapy is currently based on macrolides, quinolones, or a combination of the two, with prolonged treatment in severe cases.

Conclusions
Numerous factors influence the mortality rate of LD, such as ICU admission, the underlying immune status, and the nosocomial source of the infection. The host immune response (hyperinflammation and/or immunoparalysis) may also be associated with increased severity. Given that the incidence of LD is rising, studies on specific biomarkers of severity may be of great interest. Further assessments comparing different regimens and/or evaluating host-directed therapies are nowadays needed.

Graphical Abstract
Personalised learning in higher education for health sciences: a scoping review protocol
Authors: Ali Majid , Wahab Izyan Binti A. , Huri Hasniza Zaman , Yusoff Muhamad Saiful 
Published: April 2024

Abstract
Background
Personalised learning, an educational approach that tailors teaching and learning to individual needs and preferences, has gained attention in recent years, particularly in higher education. Advances in educational technology have facilitated the implementation of personalised learning in various contexts. Despite its potential benefits, the literature on personalised learning in health sciences higher education remains scattered and heterogeneous. This scoping review aims to identify and map the current literature on personalised learning in health sciences higher education and its definition, implementation strategies, benefits, and limitations.

Methods
A comprehensive search of electronic databases, PubMed, Scopus, Google Scholar, Educational Research Complete, and Journal Storage (JSTOR), will be conducted to identify relevant articles. The search will be limited to articles published in the English language between 2000 and 2023. The search strategy will be designed and adapted for each database using a combination of keywords and subject headings related to personalised learning and health sciences higher education. Eligibility criteria will be applied to screen and select articles. Data extraction and quality assessment will be performed, and thematic synthesis will be used to analyse the extracted data.

Discussion
The results of the scoping review will present a comprehensive and coherent overview of the literature on personalised learning in health sciences higher education. Key themes and topics related to personalised learning, its definitions, models, implementation strategies, benefits, and limitations, will be identified. The geographical and temporal distribution of research on personalised learning in health sciences higher education will also be described. This scoping review will provide a structured synthesis of the available evidence on personalised learning in health sciences higher education, highlighting potential gaps and areas for future research. The findings will contribute to ongoing scholarly and policy debates on personalised learning in higher education, informing the development of best practices, guidelines, and future research agendas.
Bullen-type inequalities for twice-differentiable functions by using conformable fractional integrals
Authors: Hezenci Fatih , Budak Hüseyin 
Published: April 2024

AbstractIn this paper, we prove an equality for twice-differentiable convex functions involving the conformable fractional integrals. Moreover, several Bullen-type inequalities are established for twice-differentiable functions. More precisely, conformable fractional integrals are used to derive such inequalities. Furthermore, sundry significant inequalities are obtained by taking advantage of the convexity, Hölder inequality, and power-mean inequality. Finally, we provide our results by using special cases of obtained theorems.
Profiling the role of m6A effectors in the regulation of pluripotent reprogramming
Authors: Wang Wenjun , Zhou Lei , Li Hui , Sun Tingge , Wen Xue , Li Wei , Esteban Miguel A. , Hoffman Andrew R. , Hu Ji-Fan , Cui Jiuwei 
Published: April 2024

AbstractThe N6-methyladenosine (m6A) RNA modification plays essential roles in multiple biological processes, including stem cell fate determination. To explore the role of the m6A modification in pluripotent reprogramming, we used RNA-seq to map m6A effectors in human iPSCs, fibroblasts, and H9 ESCs, as well as in mouse ESCs and fibroblasts. By integrating the human and mouse RNA-seq data, we found that 19 m6A effectors were significantly upregulated in reprogramming. Notably, IGF2BPs, particularly IGF2BP1, were among the most upregulated genes in pluripotent cells, while YTHDF3 had high levels of expression in fibroblasts. Using quantitative PCR and Western blot, we validated the pluripotency-associated elevation of IGF2BPs. Knockdown of IGF2BP1 induced the downregulation of stemness genes and exit from pluripotency. Proteome analysis of cells collected at both the beginning and terminal states of the reprogramming process revealed that the IGF2BP1 protein was positively correlated with stemness markers SOX2 and OCT4. The eCLIP-seq target analysis showed that IGF2BP1 interacted with the coding sequence (CDS) and 3’UTR regions of the SOX2 transcripts, in agreement with the location of m6A modifications. This study identifies IGF2BP1 as a vital pluripotency-associated m6A effector, providing new insight into the interplay between m6A epigenetic modifications and pluripotent reprogramming.
Understanding the impact of essential oils on grape metabolism and pathogen resistance: a study with a focus on Botrytis cinerea
Authors: Kaya Ozkan , Karakus Sinem , Bozkurt Abdurrahim , Yilmaz Turhan , Hajizadeh Hanifeh Seyed , Turan Metin 
Published: April 2024

Abstract
Background
The exploration of EOs and their impact on primary metabolites in agricultural products, such as grapes, holds significant importance in the post-harvest preservation and enhancement of berry quality. Therefore, our research aimed to dissect the effects of various EO treatments on the biochemical composition of grapes, specifically examining alterations in sugar, organic acid, and amino acid levels.

Results
Our findings highlighted that the OF treatment, a combination of Eugenol and Botrytis cinerea, significantly escalated sugar content, with remarkable increases in sucrose, glucose, and fructose compared to the control group. The SF treatment led to the highest levels of certain organic acids, including tartaric, butyric, and malonic acids, whereas the TO treatment prominently augmented amino acids such as tyrosine and phenylalanine. Utilizing PCA, our study effectively captured the variability within the treatment dataset, revealing distinct clusters of treatments and their correlations with specific metabolites. The PCA biplot underscored the influence of treatments on metabolic profile of grape berries, with treatments like OSF, TO, and TOSF demonstrating close associations with specific amino acids, suggesting positive correlations.

Conclusion
Our current results indicate that EOs substantial influence on the metabolic profile of grapes, resulting in enhanced fruit quality and extended shelf life. Variations in sugar, organic acid, and amino acid levels among different EO treatments highlight their potential for improving post-harvest characteristics. To sum up, these findings are valuable for the agricultural and food industries, showcasing the utility of EOs as natural preservatives and enhancers in fruit cultivation and storage.

Graphical Abstract