bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of tumor location with anxiety and depression in childhood brain cancer survivors: a systematic review and meta-analysis
Authors: Szabados Márton , Kolumbán Erika , Agócs Gergely , Kiss-Dala Szilvia , Engh Marie Anne , Hernádfői Márk , Takács Kata , Tuboly Eszter , Párniczky Andrea , Hegyi Péter , Garami Miklós 
Published: October 2023

Abstract
Objective
This study aimed to evaluate the association between the location (supratentorial or infratentorial) of brain tumors and the development of depression and anxiety in childhood cancer survivors. Understanding the risk factors for the development of depression and anxiety disordersin these patients is crucial for early diagnosis and successful treatment.

Methods
The meta-analysis included articles that listed patients diagnosed with an intracranial tumor before the age of 18 years, provided the location of the tumor, had exact data on the prevalence of anxiety and depression, or measured these disorders using different assessment tools. The search was conducted in five different databases (MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library). Risk of bias was assessed using QUIPS-2. Outcome measures used were prevalences and standardized means.

Results
The analysis included 42 eligible articles with a total number of 1071 patients. Relevant articles were cohort studies, cross-sectional studies, and case series. Based on the available data infratentorial brain tumor survivors had significantly higher scores on various assessment tools measuring anxiety (MRAW (raw mean scores): 36.24 [CI (confidence interval): 28.81–43.67]; versus MRAW: 23.21 (CI 0.91–45.51); p = 0.02, and depression (MRAW: 27.57 (CI 14.35–40.78) versus MRAW: 13.84 (CI 11.43–16.26); p < 0.01.

Conclusion
Childhood infratentorial cancer survivors have more impairments in terms of depression and anxiety; these children and adults should be monitored more frequently and may require closer follow-up on their mental health. The main limitation of our study originates from the lack of data on follow-up times used by different studies.
FOVOCIP study: a multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients—efficacy and microbiologic safety
Authors: Moreno Ainhoa Fernández , Lavín-Alconero Lucía , de Ugarriza Paula López , Blanco Laura Solán , Hernández Sara Cáceres , Burgués Juan Miguel Bergua , de Miguel María Izquierdo , Huerta Ana Julia González , Zarzuela Marta Polo , Boluda Blanca , Humala Karem , Calabuig Maria Luisa , Amigo Maria Luz , Casas Marián Cuesta , del Mar García-Saiz María , Verdugo Ana Fernández , Domínguez Javier Fernández , Bernal Teresa 
Published: October 2023

Abstract
Background
Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient’s mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB.

Methods
A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed.

Discussion
This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated.

Trial registration
Clinical trials NCT05311254, Registered on 5 April 2022, https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&cntry=ES&draw=2&rank=1. Protocol version: 3.0, dated 20 May 2022.
Multidimensional optimization for accelerating light-powered biocatalysis in Rhodopseudomonas palustris
Authors: Zhang Yang , Meng Wenchang , He Yuting , Chen Yuhui , Shao Mingyu , Yuan Jifeng 
Published: October 2023

Abstract
Background
Whole-cell biocatalysis has been exploited to convert a variety of substrates into high-value bulk or chiral fine chemicals. However, the traditional whole-cell biocatalysis typically utilizes the heterotrophic microbes as the biocatalyst, which requires carbohydrates to power the cofactor (ATP, NAD (P)H) regeneration.

Results
In this study, we sought to harness purple non-sulfur photosynthetic bacterium (PNSB) as the biocatalyst to achieve light-driven cofactor regeneration for cascade biocatalysis. We substantially improved the performance of Rhodopseudomonas palustris-based biocatalysis using a highly active and conditional expression system, blocking the side-reactions, controlling the feeding strategy, and attenuating the light shading effect. Under light-anaerobic conditions, we found that 50 mM ferulic acid could be completely converted to vanillyl alcohol using the recombinant strain with 100% efficiency, and > 99.9% conversion of 50 mM p-coumaric acid to p-hydroxybenzyl alcohol was similarly achieved. Moreover, we examined the isoprenol utilization pathway for pinene synthesis and 92% conversion of 30 mM isoprenol to pinene was obtained.

Conclusions
Taken together, these results suggested that R. palustris could be a promising host for light-powered biotransformation, which offers an efficient approach for synthesizing value-added chemicals in a green and sustainable manner.

Graphical Abstract
Seasonal dynamics of Amblyomma cajennense (Fabricius, 1787) sensu stricto in a degraded area of the Amazon biome, with notes on Rickettsia amblyommatis infection
Authors: de Araújo Flávio Eduardo Saraiva , Martins Thiago Fernandes , Ramos Carlos Celso Mendonça , Nogueira Rafael Michael Silva , Faccini João Luiz Horacio , Tavares Mariana Avelar , de Lima Nicolas Jalowitzki , de Almeida Júnior Eduardo Bezerra , de Sousa-Paula Lucas Christian , Dantas-Torres Filipe , da Silva Krawczak Felipe , Costa-Junior Livio Martins , Labruna Marcelo Bahia , Dall′Agnol Leonardo Teixeira , Luz Hermes Ribeiro 
Published: October 2023

Abstract
Background
The tick Amblyomma cajennense sensu stricto (A. cajennense s.s.) frequently parasitizes animals and humans in the Amazon biome, in addition to being a vector of Rickettsia amblyommatis. In the present study, we evaluated both the population dynamics of A. cajennense s.s. in a degraded area of the Amazon biome and the presence of rickettsial organisms in this tick population.

Methods
The study was carried out in a rural area of the Santa Inês municipality (altitude: 24 m a.s.l.), Maranhão state, Brazil. Ticks were collected from the environment for 24 consecutive months, from June 2021 to May 2023. The region is characterized by two warm seasons: a rainy season (November–May) and a dry season (June–October). We characterized the temporal activity of A. cajennense s.s. on the vegetation by examining questing activity for each life stage (larvae, nymphs, adults [males and females]) in relation to the dry and rainy season. Ticks collected in this study were randomly selected and individually tested by a TaqMan real-time PCR assay that targeted a 147-bp fragment of the rickettsial gltA gene.

Results
Overall, 1843 (62.4%) adults (52.6% females, 47.4% males), 1110 (37.6%) nymphs and 398 larval clusters were collected. All adult females and nymphs were morphologically identified as A. cajennense s.s. Larval activity was observed from April to December, with a peak from June to September (dry season); nymph abundance peaked from September to November (transition period between dry and rainy seasons); and adult ticks were abundant from October to May (spring/summer/early autumn). The infection rate by R. amblyommatis in A. cajennense s.s. ticks was at least 7% (7/99).

Conclusion
Our data suggest a 1-year generation pattern for A. cajennense s.s., with a well-defined seasonality of larvae, nymphs and adults in the Amazon biome. Larvae predominate during the dry season, nymphs are most abundant in the dry-rainy season transition and adults are most abundant in the rainy season. The presence of R. amblyommatis in adult ticks suggests that animals and humans in the study region are at risk of infection by this species belonging to the spotted fever group of Rickettsia.

Graphical Abstract
Profound DNA methylomic differences between single- and multi-fraction alpha irradiations of lung fibroblasts
Authors: Vera-Chang Marilyn N. , Danforth John M. , Stuart Marilyne , Goodarzi Aaron A. , Brand Marjorie , Richardson Richard B. 
Published: October 2023

Abstract
Background
Alpha (α)-radiation is a ubiquitous environmental agent with epigenotoxic effects. Human exposure to α-radiation at potentially harmful levels can occur repetitively over the long term via inhalation of naturally occurring radon gas that accumulates in enclosed spaces, or as a result of a single exposure from a nuclear accident. Alterations in epigenetic DNA methylation (DNAm) have been implicated in normal aging and cancer pathogenesis. Nevertheless, the effects of aberrations in the methylome of human lung cells following exposure to single or multiple α-irradiation events on these processes remain unexplored.

Results
We performed genome-wide DNAm profiling of human embryonic lung fibroblasts from control and irradiated cells using americium-241 α-sources. Cells were α-irradiated in quadruplicates to seven doses using two exposure regimens, a single-fraction (SF) where the total dose was given at once, and a multi-fraction (MF) method, where the total dose was equally distributed over 14 consecutive days. Our results revealed that SF irradiations were prone to a decrease in DNAm levels, while MF irradiations mostly increased DNAm. The analysis also showed that the gene body (i.e., exons and introns) was the region most altered by both the SF hypomethylation and the MF hypermethylation. Additionally, the MF irradiations induced the highest number of differentially methylated regions in genes associated with DNAm biomarkers of aging, carcinogenesis, and cardiovascular disease. The DNAm profile of the oncogenes and tumor suppressor genes suggests that the fibroblasts manifested a defensive response to the MF α-irradiation. Key DNAm events of ionizing radiation exposure, including changes in methylation levels in mitochondria dysfunction-related genes, were mainly identified in the MF groups. However, these alterations were under-represented, indicating that the mitochondria undergo adaptive mechanisms, aside from DNAm, in response to radiation-induced oxidative stress.

Conclusions
We identified a contrasting methylomic profile in the lung fibroblasts α-irradiated to SF compared with MF exposures. These findings demonstrate that the methylome response of the lung cells to α-radiation is highly dependent on both the total dose and the exposure regimen. They also provide novel insights into potential biomarkers of α-radiation, which may contribute to the development of innovative approaches to detect, prevent, and treat α-particle-related diseases.

Graphical abstract
Peripheral blood DNA methylation and neuroanatomical responses to HDACi treatment that rescues neurological deficits in a Kabuki syndrome mouse model
Authors: Goodman Sarah Jessica , Luperchio Teresa Romeo , Ellegood Jacob , Chater-Diehl Eric , Lerch Jason P. , Bjornsson Hans Tomas , Weksberg Rosanna 
Published: October 2023

Abstract
Background
Recent findings from studies of mouse models of Mendelian disorders of epigenetic machinery strongly support the potential for postnatal therapies to improve neurobehavioral and cognitive deficits. As several of these therapies move into human clinical trials, the search for biomarkers of treatment efficacy is a priority. A potential postnatal treatment of Kabuki syndrome type 1 (KS1), caused by pathogenic variants in KMT2D encoding a histone-lysine methyltransferase, has emerged using a mouse model of KS1 (Kmt2d+/βGeo). In this mouse model, hippocampal memory deficits are ameliorated following treatment with the histone deacetylase inhibitor (HDACi), AR-42. Here, we investigate the effect of both Kmt2d+/βGeo genotype and AR-42 treatment on neuroanatomy and on DNA methylation (DNAm) in peripheral blood. While peripheral blood may not be considered a “primary tissue” with respect to understanding the pathophysiology of neurodevelopmental disorders, it has the potential to serve as an accessible biomarker of disease- and treatment-related changes in the brain.

Methods
Half of the KS1 and wildtype mice were treated with 14 days of AR-42. Following treatment, fixed brain samples were imaged using MRI to calculate regional volumes. Blood was assayed for genome-wide DNAm at over 285,000 CpG sites using the Illumina Infinium Mouse Methylation array. DNAm patterns and brain volumes were analyzed in the four groups of animals: wildtype untreated, wildtype AR-42 treated, KS1 untreated and KS1 AR-42 treated.

Results
We defined a DNAm signature in the blood of KS1 mice, that overlapped with the human KS1 DNAm signature. We also found a striking 10% decrease in total brain volume in untreated KS1 mice compared to untreated wildtype, which correlated with DNAm levels in a subset KS1 signature sites, suggesting that disease severity may be reflected in blood DNAm. Treatment with AR-42 ameliorated DNAm aberrations in KS1 mice at a small number of signature sites.

Conclusions
As this treatment impacts both neurological deficits and blood DNAm in mice, future KS clinical trials in humans could be used to assess blood DNAm as an early biomarker of therapeutic efficacy.
The co-occurrence of Kikuchi–Fujimoto disease and systemic lupus erythematosus: a case report
Authors: Yousefi Maysam , Rukerd Mohammad Rezaei Zadeh , Binafar Hanieh , Shoaie Sahar , Mirkamali Hanieh , Pourzand Pouria , Kaveh Roxana 
Published: October 2023

Abstract
Background
Kikuchi–Fujimoto disease is an uncommon systemic disease that mostly affects young women. Kikuchi–Fujimoto disease typically manifests as necrotizing lymphadenopathy, which frequently follows by a fever; however, Kikuchi–Fujimoto disease occurs rarely in extranodal regions. One of the most important accompaniments of Kikuchi–Fujimoto disease is its connection with autoimmune diseases such as systemic lupus erythematosus. This case presents a simultaneous occurrence of Kikuchi–Fujimoto disease with liver involvement and systemic lupus erythematosus in a young female patient.

Case presentation
We present a rare case of a 20-year-old white woman who presented with fever, joint pains, myalgia, and shortness of breath. Initial hospitalization and treatment for fever of unknown origin did not yield improvement. Physical examination revealed cervical and supraclavicular lymphadenopathy, and laboratory investigations showed abnormal blood counts, elevated inflammatory markers, and positive autoimmune serologies. Imaging studies revealed bilateral pleural effusion and liver lesions. Lymph node biopsy confirmed the diagnosis of Kikuchi–Fujimoto disease, and liver biopsy showed extranodal involvement. The patient was diagnosed with Kikuchi–Fujimoto disease-associated systemic lupus erythematosus and treated with hydroxychloroquine and corticosteroids. The patient showed gradual resolution of symptoms and lymphadenopathy with treatment.

Conclusion
Kikuchi–Fujimoto disease is a rare systemic condition primarily impacting young females. It is characterized by necrotizing lymphadenopathy, often accompanied by fever. Although Kikuchi–Fujimoto disease is predominantly seen in the lymph nodes, occurrences in non-nodal areas are infrequent. When diagnosing Kikuchi–Fujimoto disease, it is essential to screen patients for systemic lupus erythematosus. In this particular case, we observed liver involvement along with the presence of both Kikuchi–Fujimoto disease and systemic lupus erythematosus.
Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway
Authors: Zheng Xiang , Yang Lei , Zhai Wei , Geng Nana , Zhang Zhimin , Li Xueying , Wu Mingsong 
Published: October 2023

Abstract
Background
Cisplatin (CDDP) is a common anticancer drug whose side effects limit its clinical applications. Tannins (TA) are plant-derived polyphenols that inhibit tumor growth in different types of cancer. Here, we evaluated the anticancer effect of TA combined with CDDP on lung cancer cell lines (GLC-82 and H1299) and investigated the underlying molecular mechanism of endoplasmic reticulum (ER) stress-induced apoptosis.

Methods
Cell lines were treated with CDDP, TA, and CDDP + TA, and the effect of the combination was assessed using MTT assay and observed under light and fluorescence microscopes. Cell apoptosis was detected by flow cytometry, and the levels of ERS apoptosis pathway related genes were valuated by qRT-PCR and western blotting. The effects of the drug combination on the tumors of nude mice injected with H1299 cells were investigated, and the expression of key factors in the ER stress apoptotic pathway was investigated.

Results
The combination of CDDP and TA significantly inhibited lung cancer cell viability indicating a synergistic antitumoral effect. The mRNA and protein expression levels of key ER stress factors in the CDDP + TA group were considerably higher than those in the CDDP and TA groups, the tumor volume in tumor-bearing mice was the smallest, and the number of apoptotic cells and the protein expression levels of the key ER stress in the combination group were considerably higher.

Conclusions
The combination of TA and CDDP may produce synergistic antitumoral effects mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer.
A transformer-based multi-task deep learning model for simultaneous infiltrated brain area identification and segmentation of gliomas
Authors: Li Yin , Zheng Kaiyi , Li Shuang , Yi Yongju , Li Min , Ren Yufan , Guo Congyue , Zhong Liming , Yang Wei , Li Xinming , Yao Lin 
Published: October 2023

Abstract
Background
The anatomical infiltrated brain area and the boundaries of gliomas have a significant impact on clinical decision making and available treatment options. Identifying glioma-infiltrated brain areas and delineating the tumor manually is a laborious and time-intensive process. Previous deep learning-based studies have mainly been focused on automatic tumor segmentation or predicting genetic/histological features. However, few studies have specifically addressed the identification of infiltrated brain areas. To bridge this gap, we aim to develop a model that can simultaneously identify infiltrated brain areas and perform accurate segmentation of gliomas.

Methods
We have developed a transformer-based multi-task deep learning model that can perform two tasks simultaneously: identifying infiltrated brain areas segmentation of gliomas. The multi-task model leverages shaped location and boundary information to enhance the performance of both tasks. Our retrospective study involved 354 glioma patients (grades II-IV) with single or multiple brain area infiltrations, which were divided into training (N = 270), validation (N = 30), and independent test (N = 54) sets. We evaluated the predictive performance using the area under the receiver operating characteristic curve (AUC) and Dice scores.

Results
Our multi-task model achieved impressive results in the independent test set, with an AUC of 94.95% (95% CI, 91.78–97.58), a sensitivity of 87.67%, a specificity of 87.31%, and accuracy of 87.41%. Specifically, for grade II-IV glioma, the model achieved AUCs of 95.25% (95% CI, 91.09–98.23, 84.38% sensitivity, 89.04% specificity, 87.62% accuracy), 98.26% (95% CI, 95.22–100, 93.75% sensitivity, 98.15% specificity, 97.14% accuracy), and 93.83% (95%CI, 86.57–99.12, 92.00% sensitivity, 85.71% specificity, 87.37% accuracy) respectively for the identification of infiltrated brain areas. Moreover, our model achieved a mean Dice score of 87.60% for the whole tumor segmentation.

Conclusions
Experimental results show that our multi-task model achieved superior performance and outperformed the state-of-the-art methods. The impressive performance demonstrates the potential of our work as an innovative solution for identifying tumor-infiltrated brain areas and suggests that it can be a practical tool for supporting clinical decision making.
Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group
Authors: Rabin Karen R. , Devidas Meenakshi , Chen Zhiguo , Ji Lingyun , Kairalla John , Hitzler Johann K. , Yang Jun J. , Carroll Andrew J. , Heerema Nyla A. , Borowitz Michael J. , Wood Brent L. , Roberts Kathryn G. , Mullighan Charles G. , Harvey Richard C. , Chen I-Ming , Willman Cheryl L. , Reshmi Shalini C. , Gastier-Foster Julie M. , Bhojwani Deepa , Rheingold Susan R. , Maloney Kelly W. , Mattano Leonard A. , Larsen Eric C. , Schore Reuven J. , Burke Michael J. , Salzer Wanda L. , Winick Naomi J. , Carroll William L. , Raetz Elizabeth A. , Loh Mignon L. , Hunger Stephen P. , Angiolillo Anne L. 
Published: October 2023

PURPOSE Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019. METHODS We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials. RESULTS Patients with DS exhibited more frequent minimal residual disease (MRD) ≥0.01% at end induction (30.8% v 21.5%; P < .001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% v 11.7%; P < .0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% v 87.5% ± 0.3%; P < .0001; OS, 86.8% ± 1.4% v 93.6% ± 0.2%; P < .0001), and within NCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 × 103/μL, and end-induction MRD ≥0.01%, but not cytogenetics or CRLF2 overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% v 9.1% ± 0.2%; P = .0008), death in remission (4.9% ± 0.8% v 1.7% ± 0.1%; P < .0001), and induction death (3.4% v 0.8%; P < .0001). Mucositis, infections, and hyperglycemia were significantly more frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% v 1.8%; P = .005). CONCLUSION Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.