bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of dual STRN-NTRK2 rearrangements in a high grade sarcoma, with good clinical response to first-line larotrectinib therapy
Authors: Lin Ruihe , Mallick Atrayee Basu , Wang Zi-Xuan , Brown Scot Andrew , Lu Bo , Jiang Wei 
Published: October 2023

Abstract
Background
Among the three NTRK genes, NTRK2 possesses a tremendous structural complexity and involves tumorigenesis of several types of tumors. To date, only STRN and RBPMS are identified in the fusion with NTRK2 in adult soft tissue tumors. More recently, the highly selective Trk tyrosine kinases inhibitors, including larotrectinib and entrectinib, have shown significant efficacy for treating tumors harboring NTRK fusions and were approved by FDA.

Case presentation
We report a case of sarcoma in a 35-year-old female harboring two STRN-NTRK2 gene fusions, with a good clinical response to first-line larotrectinib treatment. Core biopsy of the 16.5 cm gluteal mass showed a high-grade mesenchymal neoplasm with features reminiscent of a solitary fibrous tumor, but negative for STAT6. In-house next-generation sequencing gene fusion panel showed two in-frame STRN-NTRK2 fusions, which contain the same 5’ partner sequence (exon 1–3) of STRN, and the 3’ fusion partner starting from either the exon 15 or the exon 16 of NTRK2. Due to the large size and location of the tumor, first-line neoadjuvant therapy with larotrectinib was initiated. The patient has an excellent clinical response with an 83% tumor size reduction by imaging. The tumor was subsequently completely resected. After 130 days, larotrectinib was reinitiated for lung metastasis (up to 7 cm), and a complete resolution was achieved. When compared with NTRK1 and NTRK3, NTRK2 fusions are the least common. Of note, the only other report in the literature on NRTK2 fusion-positive sarcoma also showed solitary fibrous tumor (SFT)-like morphology, and the patient responded well to larotrectinib as the second line adjuvant therapy.

Conclusions
In conclusion, the identification of NTRK2 fusions in patients with soft tissue tumors could significantly improve the clinical outcome through selective NTRK inhibitor therapy, especially in the first-line setting. Prompt RNA-based NGS testing at initial diagnosis may benefit these patients. Our case is among the first few in the literature on NTRK2 fusion sarcoma with first-line larotrectinib therapy in the primary and metastatic setting, with good clinical response and minimal side effects.
E3 ligase TRIM28 promotes anti-PD-1 resistance in non-small cell lung cancer by enhancing the recruitment of myeloid-derived suppressor cells
Authors: Liang Manman , Sun Zhengui , Chen Xingwu , Wang Lijing , Wang Hanli , Qin Lilong , Zhao Wenying , Geng Biao 
Published: October 2023

AbstractBackgroundAlterations in several tripartite motif-containing (TRIM) family proteins have been implicated in the pathogenesis of lung cancer. TRIM28, a member of the TRIM E3 ligase family, has been associated with tumorigenesis, cell proliferation, and inflammation. However, little is known about TRIM28 expression and its role in the immune microenvironment of non-small cell lung cancer (NSCLC).MethodsWe assessed the clinical significance of TRIM28 in tissue microarrays and TCGA cohorts. We investigated the function of TRIM28 in syngeneic mouse tumor models, theKrasLSL−G12D/+;Tp53fl/fl(KP) mouse model, and humanized mice. Immune cell composition was analyzed using flow cytometry and immunohistochemistry.ResultsOur findings revealed a positive correlation between TRIM28 expression and the infiltration of suppressive myeloid-derived suppressor cells (MDSCs) in NSCLC. Moreover, silencing TRIM28 enhanced the efficacy of anti-PD-1 immunotherapy by reshaping the inflamed tumor microenvironment. Mechanistically, we demonstrated that TRIM28 could physically interact with receptor-interacting protein kinase 1 (RIPK1) and promote K63-linked ubiquitination of RIPK1, which is crucial for sustaining activation of the NF-κB pathway. Mutagenesis of the E3 ligase domain corroborated the essential role of E3 ligase activity in TRIM28-mediated NF-κB activation. Further experiments revealed that TRIM28 could upregulate the expression of CXCL1 by activating NF-κB signaling. CXCL1 could bind to CXCR2 on MDSCs and promote their migration to the tumor microenvironment. TRIM28 knockdown increased responsiveness to anti-PD-1 therapy in immunocompetent mice, characterized by increased CD8+T tumor-infiltrating lymphocytes and decreased MDSCs.ConclusionThe present study identified TRIM28 as a promoter of chemokine-driven recruitment of MDSCs through RIPK1-mediated NF-κB activation, leading to the suppression of infiltrating activated CD8+T cells and the development of anti-PD-1 resistance. Understanding the regulation of MDSC recruitment and function by TRIM28 provides crucial insights into the association between TRIM28 signaling and the development of an immunosuppressive tumor microenvironment. These insights may inform the development of combination therapies to enhance the effectiveness of immune checkpoint blockade therapy in NSCLC.
Creating the ICU of the future: patient-centred design to optimise recovery
Authors: Tronstad Oystein , Flaws Dylan , Patterson Sue , Holdsworth Robert , Fraser John F. 
Published: October 2023

AbstractBackgroundIntensive Care survival continues to improve, and the number of ICU services is increasing globally. However, there is a growing awareness of the detrimental impact of the ICU environment on patients, families, and staff. Excessive noise and suboptimal lighting especially have been shown to adversely impact physical and mental recovery during and after an ICU admission. Current ICU designs have not kept up with advances in medical technology and models of care, and there is no current ‘gold-standard’ ICU design. Improvements in ICU designs are needed to optimise care delivery and patient outcomes.MethodsThis manuscript describes a mixed-methods, multi-staged participatory design project aimed at redesigning and implementing two innovative ICU bedspaces. Guided by the action effect method and the consolidated framework for implementation research, the manuscript describes the processes taken to ensure the patient-centred problems were properly understood, the steps taken to develop and integrate solutions to identified problems, and the process of implementation planning and rebuilding in a live ICU.ResultsTwo innovative ICU bedspaces were rebuilt and implemented. They feature solutions to address all identified problems, including noise reduction, optimisation of lighting, access to nature via digital solutions, and patient connectivity and engagement, with solutions developed from various specialty fields, including IT improvements, technological innovations, and design and architectural solutions. Early evaluation demonstrates an improved lighting and acoustic environment.ConclusionsOptimising the ICU bedspace environment and improving the lighting and acoustic environment is possible. The impact on patient outcomes needs to be evaluated.
Metabolic engineering of Thermoanaerobacterium aotearoense strain SCUT27 for biofuels production from sucrose and molasses
Authors: Dai Kaiqun , Qu Chunyun , Feng Jun , Lan Yang , Fu Hongxin , Wang Jufang 
Published: October 2023

Abstract
Background
Sucrose-rich sugarcane trash surpasses 28 million tons globally per year. Effective biorefinery systems could convert these biomasses to bioproducts, such as bioethanol from sugarcane sucrose in Brazil. Thermophilic microbes for biofuels have attracted great attention due to their higher fermentation temperature and wide substrate spectrum. However, few thermophiles using sucrose or molasses for biofuels production was reported. Thermoanaerobacterium aotearoense SCUT27 has been considered as an efficient ethanol producer, but it cannot directly utilize sucrose. In this study, various sucrose metabolic pathways were introduced and analyzed in Thermoanaerobaterium.

Results
The sucrose-6-phosphate hydrolase (scrB), which was from a screened strain Thermoanaerobacterium thermosaccharolyticum G3-1 was overexpressed in T. aotearoense SCUT27 and endowed this strain with the ability to utilize sucrose. In addition, overexpression of the sucrose-specific PTS system (scrA) from Clostridium acetobutylicum accelerated the sucrose transport. To strengthen the alcohols production and substrates metabolism, the redox-sensing transcriptional repressor (rex) in T. aotearoense was further knocked out. Moreover, with the gene arginine repressor (argR) deleted, the ethanologenic mutant P8S10 showed great inhibitors-tolerance and finally accumulated ~ 34 g/L ethanol (a yield of 0.39 g/g sugars) from pretreated cane molasses in 5 L tank by fed-batch fermentation. When introducing butanol synthetic pathway, 3.22 g/L butanol was produced by P8SB4 with a yield of 0.44 g alcohols/g sugars at 50℃. This study demonstrated the potential application of T. aotearoense SCUT27 for ethanol and butanol production from low cost cane molasses.

Conclusions
Our work provided strategies for sucrose utilization in thermophiles and improved biofuels production as well as stress tolerances of T. aotearoense SCUT27, demonstrating the potential application of the strain for cost-effective biofuels production from sucrose-based feedstocks.
N6-methyladenosine methylation in kidney injury
Authors: Wang Qimeng , Fan Xiaoting , Sheng Qinghao , Yang Meilin , Zhou Ping , Lu Shangwei , Gao Ying , Kong Zhijuan , Shen Ning , Lv Zhimei , Wang Rong 
Published: October 2023

AbstractMultiple mechanisms are involved in kidney damage, among which the role of epigenetic modifications in the occurrence and development of kidney diseases is constantly being revealed. However, N6-methyladenosine (M6A), a well-known post-transcriptional modification, has been regarded as the most prevalent epigenetic modifications in higher eukaryotic, which is involved in various biological processes of cells such as maintaining the stability of mRNA. The role of M6A modification in the mechanism of kidney damage has attracted widespread attention. In this review, we mainly summarize the role of M6A modification in the progression of kidney diseases from the following aspects: the regulatory pattern of N6-methyladenosine, the critical roles of N6-methyladenosine in chronic kidney disease, acute kidney injury and renal cell carcinoma, and then reveal its potential significance in the diagnosis and treatment of various kidney diseases. A better understanding of this field will be helpful for future research and clinical treatment of kidney diseases.
Further refinement of the differentially methylated distant lung-specific FOXF1 enhancer in a neonate with alveolar capillary dysplasia
Authors: Szafranski Przemyslaw , Garimella Rijutha P. , Mani Haresh , Hartman Ryan , Deutsch Gail , Silk Alan , Benheim Alan , Stankiewicz Paweł 
Published: October 2023

AbstractHeterozygous SNVs or CNV deletions involving the FOXF1 gene, or its distant enhancer, are causative for 80–90% of cases of alveolar capillary dysplasia with misalignment of pulmonary veins. Recently, we proposed bimodal structure and parental functional dimorphism of the lung-specific FOXF1 enhancer, with Unit 1 having higher activity on the paternal chr16 and Unit 2 on the maternal chr16. Here, we describe a novel unusually sized pathogenic de novo copy-number variant deletion involving a portion of the FOXF1 enhancer on maternal chr16 that implies narrowing Unit 2 to an essential ~ 9-kb segment. Using a restrictase-based assay, we found that this enhancer segment is weakly methylated at ApT adenine, with about twice the frequency of methylation on the maternal versus paternal chr16. Our data provide further insight into the FOXF1 enhancer structure and function.
Art driven by visual representations of chemical space
Authors: Gaytán-Hernández Daniela , Chávez-Hernández Ana L. , López-López Edgar , Miranda-Salas Jazmín , Saldívar-González Fernanda I. , Medina-Franco José L. 
Published: October 2023

AbstractScience and art have been connected for centuries. With the development of new computational methods, new scientific disciplines have emerged, such as computational chemistry, and related fields, such as cheminformatics. Chemoinformatics is grounded on the chemical space concept: a multi-descriptor space in which chemical structures are described. In several practical applications, visual representations of the chemical space of compound datasets are low-dimensional plots helpful in identifying patterns. However, the authors propose that the plots can also be used as artistic expressions. This manuscript introduces an approach to merging art with chemoinformatics through visual and artistic representations of chemical space. As case studies, we portray the chemical space of food chemicals and other compounds to generate visually appealing graphs with twofold benefits: sharing chemical knowledge and developing pieces of art driven by chemoinformatics. The art driven by chemical space visualization will help increase the application of chemistry and art and contribute to general education and dissemination of chemoinformatics and chemistry through artistic expressions. All the code and data sets to reproduce the visual representation of the chemical space presented in the manuscript are freely available at https://github.com/DIFACQUIM/Art-Driven-by-Visual-Representations-of-Chemical-Space-.Scientific contribution: Chemical space as a concept to create digital art and as a tool to train and introduce students to cheminformatics.
Graphical Abstract
Effects of hTERT transfection on the telomere and telomerase of Periplaneta americana cells in vitro
Authors: Ma Chenjing , Li Xian , Ding Weifeng , Zhang Xin , Chen Hang , Feng Ying 
Published: October 2023

AbstractTelomere and telomerase are crucial factors in cell division and chromosome stability. Telomerase activity in most cells depends on the transcription control by the telomerase reverse transcriptase (TERT). The introduction of an exogenous human TERT (hTERT) in cultured cells could enhance telomerase activity and elongate the lifespan of various cells. Telomere elongation mechanisms vary between insects and are complex and unusual. Whether the use of exogenous hTERT can immortalize primary insect cells remains to be investigated. In this study, we used a recombinant virus expressing hTERT to infect primary cultured cells of Periplaneta americana and evaluated its effects on insect cell immortalization. We found that hTERT was successfully expressed and promoted the growth of P. americana cells, shortening their doubling time. This was due to the ability of hTERT to increase the activity of telomerase in P. americana cells, thus prolonging the telomeres. Our study lays the foundation for understanding the mechanisms of telomere elongation in P. americana, and suggests that the introduction of hTERT into insect cells could be an efficient way to establish certain insect cell lines.
GHB: a life-threatening drug complications and outcome of GHB detoxification treatment—an observational clinical study
Authors: Neu Peter , Danker-Hopfe Heidi , Fisher Robert , Ehlen Felicitas 
Published: October 2023

Abstract
Background
GHB (gammahydroxybutyrate) and its precursors are popular recreational drugs due to their sedative, anxiolytic and sexually stimulating effects. Their use has been steadily increasing in recent years. The detoxification process is complex and prone to high rates of complications while little is known about the pathophysiology. This study aims to elucidate the characteristics of GHB-addicted patients and to evaluate the risks and complications of GHB withdrawal treatment.

Methods
This observational study describes prospectively the socioeconomic status, clinical history and course of inpatient detoxification treatment of a group of 39 patients suffering from GHB substance use disorder. Detoxification treatment took place in a highly specialized psychiatric inpatient unit for substance use disorders.

Results
GHB patients were characterised by being young, well-educated and by living alone. More than 50% of the patients had no regular income. The patients were male and female in equal numbers. Detoxification treatment was complicated, with high rates of delirium (30.8%) and high need for intensive care (20.5%).

Conclusions
In our sample, GHB users were young, well-educated people and male and female in equal number. Detoxification proved to be dangerous for GHB-addicted patients. The presence of delirium and the need for transfer to an intensive care unit during detoxification treatment was extraordinarily high, even with appropriate clinical treatment. The reasons for this remain unknown. Therefore an intensive care unit should be available for GHB detoxification treatment. Further studies are needed to evaluate the options for prophylactic treatment of delirium during detoxification.
A comprehensive analysis of gut and skin microbiota in canine atopic dermatitis in Shiba Inu dogs
Authors: Thomsen Mirja , Künstner Axel , Wohlers Inken , Olbrich Michael , Lenfers Tim , Osumi Takafumi , Shimazaki Yotaro , Nishifuji Koji , Ibrahim Saleh M. , Watson Adrian , Busch Hauke , Hirose Misa 
Published: October 2023

AbstractBackgroundLike its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies. Therefore, we conducted a comprehensive analysis of both gut and skin microbiota in cAD in one specific cAD-predisposed breed, Shiba Inu. Additionally, we evaluated the impact of commonly used medical management on cAD (Janus kinase; JAK inhibitor, oclacitinib) on the gut and skin microbiota. Furthermore, we genotyped the Shiba Inu dogs according to the mitochondrial DNA haplogroup and assessed its association with the composition of the gut microbiota.ResultsStaphylococcuswas the most predominant bacterial genus observed in the skin;Escherichia/ShigellaandClostridium sensu strictowere highly abundant in the gut of cAD-affected dogs. In the gut microbiota,FusobacteriaandMegamonaswere highly abundant in healthy dogs but significantly reduced in cAD-affected dogs. The abundance of these bacterial taxa was positively correlated with the effect of the treatment and state of the disease. Oclacitinib treatment on cAD-affected dogs shifted the composition of microbiota towards that in healthy dogs, and the latter brought it much closer to healthy microbiota, particularly in the gut. Additionally, even within the same dog breed, the mtDNA haplogroup varied, and there was an association between the mtDNA haplogroup and microbial composition in the gut and skin.ConclusionsDysbiosis of both the skin and the gut was observed in cAD in Shiba Inu dogs. Our findings provide a basis for the potential treatment of cAD by manipulating the gut microbiota as well as the skin microbiota.
Global diversity and biogeography of DNA viral communities in activated sludge systems
Authors: Fan Xiangyu , Ji Mengzhi , Mu Dashuai , Zeng Xianghe , Tian Zhen , Sun Kaili , Gao Rongfeng , Liu Yang , He Xinyuan , Wu Linwei , Li Qiang 
Published: October 2023

Abstract
Background
Activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses that regulate microbial metabolism and nutrient cycling, significantly influencing the stability of AS systems. However, our knowledge about the diversity of viral taxonomic groups and functional traits in global AS systems is still limited. To address this gap, we investigated the global diversity and biogeography of DNA viral communities in AS systems using 85,114 viral operational taxonomic units (vOTUs) recovered from 144 AS samples collected across 54 WWTPs from 13 different countries.

Results
AS viral communities and their functional traits exhibited distance-decay relationship (DDR) at the global scale and latitudinal diversity gradient (LDG) from equator to mid-latitude. Furthermore, it was observed that AS viral community and functional gene structures were largely driven by the geographic factors and wastewater types, of which the geographic factors were more important. Carrying and disseminating auxiliary metabolic genes (AMGs) associated with the degradation of polysaccharides, sulfate reduction, denitrification, and organic phosphoester hydrolysis, as well as the lysis of crucial functional microbes that govern biogeochemical cycles were two major ways by which viruses could regulate AS functions. It was worth noting that our study revealed a high abundance of antibiotic resistance genes (ARGs) in viral genomes, suggesting that viruses were key reservoirs of ARGs in AS systems.

Conclusions
Our results demonstrated the highly diverse taxonomic groups and functional traits of viruses in AS systems. Viral lysis of host microbes and virus-mediated HGT can regulate the biogeochemical and nutrient cycles, thus affecting the performance of AS systems. These findings provide important insights into the viral diversity, function, and ecology in AS systems on a global scale.
Secretory IgA impacts the microbiota density in the human nose
Authors: van Dalen Rob , Elsherbini Ahmed M. A. , Harms Mareike , Alber Svenja , Stemmler Regine , Peschel Andreas 
Published: October 2023

Abstract
Background
Respiratory mucosal host defense relies on the production of secretory IgA (sIgA) antibodies, but we currently lack a fundamental understanding of how sIgA is induced by contact with microbes and how such immune responses may vary between humans. Defense of the nasal mucosal barrier through sIgA is critical to protect from infection and to maintain homeostasis of the microbiome, which influences respiratory disorders and hosts opportunistic pathogens.

Methods
We applied IgA-seq analysis to nasal microbiota samples from male and female healthy volunteers, to identify which bacterial genera and species are targeted by sIgA on the level of the individual host. Furthermore, we used nasal sIgA from the same individuals in sIgA deposition experiments to validate the IgA-seq outcomes.

Conclusions
We observed that the amount of sIgA secreted into the nasal mucosa by the host varied substantially and was negatively correlated with the bacterial density, suggesting that nasal sIgA limits the overall bacterial capacity to colonize. The interaction between mucosal sIgA antibodies and the nasal microbiota was highly individual with no obvious differences between potentially invasive and non-invasive bacterial species. Importantly, we could show that for the clinically relevant opportunistic pathogen and frequent nasal resident Staphylococcus aureus, sIgA reactivity was in part the result of epitope-independent interaction of sIgA with the antibody-binding protein SpA through binding of sIgA Fab regions. This study thereby offers a first comprehensive insight into the targeting of the nasal microbiota by sIgA antibodies. It thereby helps to better understand the shaping and homeostasis of the nasal microbiome by the host and may guide the development of effective mucosal vaccines against bacterial pathogens.