bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case study of a liver transplant-treated patient with glycogen storage disease type Ia presenting with multiple inflammatory hepatic adenomas: an analysis of clinicopathologic and genetic data
Authors: Wang Ao , Wu Jiamei , Yuan Xiaohui , Liu Jianping , Lu Changli 
Published: May 2024

Abstract
Background
Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay.

Case presentation
Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES).
WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother.
Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of β-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive.
This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation.
After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred.

Conclusion
The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.
Development of a scalable recombinant system for cyclic beta-1,2-glucans production
Authors: Guidolin L. Soledad , Caillava A. Josefina , Landoni Malena , Couto Alicia S. , Comerci Diego J. , Ciocchini Andrés E. 
Published: May 2024

Abstract
Background
Cyclic β-1,2-glucans (CβG) are bacterial cyclic homopolysaccharides with interesting biotechnological applications. These ring-shaped molecules have a hydrophilic surface that confers high solubility and a hydrophobic cavity able to include poorly soluble molecules. Several studies demonstrate that CβG and many derivatives can be applied in drug solubilization and stabilization, enantiomer separation, catalysis, synthesis of nanomaterials and even as immunomodulators, suggesting these molecules have great potential for their industrial and commercial exploitation. Nowadays, there is no method to produce CβG by chemical synthesis and bacteria that synthesize them are slow-growing or even pathogenic, which makes the scaling up of the process difficult and expensive. Therefore, scalable production and purification methods are needed to afford the demand and expand the repertoire of applications of CβG.

Results
We present the production of CβG in specially designed E. coli strains by means of the deletion of intrinsic polysaccharide biosynthetic genes and the heterologous expression of enzymes involved in CβG synthesis, transport and succinilation. These strains produce different types of CβG: unsubstituted CβG, anionic CβG and CβG of high size. Unsubstituted CβG with a degree of polymerization of 17 to 24 glucoses were produced and secreted to the culture medium by one of the strains. Through high cell density culture (HCDC) of that strain we were able to produce 4,5 g of pure unsubstituted CβG /L in culture medium within 48 h culture.

Conclusions
We have developed a new recombinant bacterial system for the synthesis of cyclic β-1,2-glucans, expanding the use of bacteria as a platform for the production of new polysaccharides with biotechnological applications. This new approach allowed us to produce CβG in E. coli with high yields and the highest volumetric productivity reported to date. We expect this new highly scalable system facilitates CβG availability for further research and the widespread use of these promising molecules across many application fields.
Flavokawain C inhibits glucose metabolism and tumor angiogenesis in nasopharyngeal carcinoma by targeting the HSP90B1/STAT3/HK2 signaling axis
Authors: Hu YuQiang , Yu ChenJie , Cheng LiangJun , Zhong Chang , An Jun , Zou MingZhen , Liu Bing , Gao Xia 
Published: May 2024

Abstract
Objective
Over the past decade, heat shock protein 90 (HSP90) inhibitors have emerged as promising anticancer drugs in solid and hematological malignancies. Flavokawain C (FKC) is a naturally occurring chalcone that has been found to exert considerable anti-tumor efficacy by targeting multiple molecular pathways. However, the efficacy of FKC has not been studied in nasopharyngeal carcinoma (NPC). Metabolic abnormalities and uncontrolled angiogenesis are two important features of malignant tumors, and the occurrence of these two events may involve the regulation of HSP90B1. Therefore, this study aimed to explore the effects of FKC on NPC proliferation, glycolysis, and angiogenesis by regulating HSP90B1 and the underlying molecular regulatory mechanisms.

Methods
HSP90B1 expression was analyzed in NPC tissues and its relationship with patient’s prognosis was further identified. Afterward, the effects of HSP90B1 on proliferation, apoptosis, glycolysis, and angiogenesis in NPC were studied by loss-of-function assays. Next, the interaction of FKC, HSP90B1, and epidermal growth factor receptor (EGFR) was evaluated. Then, in vitro experiments were designed to analyze the effect of FKC treatment on NPC cells. Finally, in vivo experiments were allowed to investigate whether FKC treatment regulates proliferation, glycolysis, and angiogenesis of NPC cells by HSP90B1/EGFR pathway.

Results
HSP90B1 was highly expressed in NPC tissues and was identified as a poor prognostic factor in NPC. At the same time, knockdown of HSP90B1 can inhibit the proliferation of NPC cells, trigger apoptosis, and reduce glycolysis and angiogenesis. Mechanistically, FKC affects downstream EGFR phosphorylation by regulating HSP90B1, thereby regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. FKC treatment inhibited the proliferation, glycolysis, and angiogenesis of NPC cells, which was reversed by introducing overexpression of HSP90B1. In addition, FKC can affect NPC tumor growth and metastasis in vivo by regulating the HSP90B1/EGFR pathway.

Conclusion
Collectively, FKC inhibits glucose metabolism and tumor angiogenesis in NPC by targeting the HSP90B1/EGFR/PI3K/Akt/mTOR signaling axis.
Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study
Authors: Guedes Mariana , Gathara David , López-Hernández Inmaculada , Pérez-Crespo Pedro María Martínez , Pérez-Rodríguez María Teresa , Sousa Adrian , Plata Antonio , Reguera-Iglesias Jose María , Boix-Palop Lucía , Dietl Beatriz , Blanco Juan Sevilla , Castillo Carlos Armiñanzas , Galán-Sánchez Fátima , Kindelán Clara Natera , Jover-Saenz Alfredo , Aguirre Josune Goikoetxea , Alemán Ana Alemán , Ciordia Teresa Marrodán , del Arco Jiménez Alfonso , Fernandez-Suarez Jonathan , Lopez-Cortes Luis Eduardo , Rodríguez-Baño Jesús ,   PROBAC/GEIRAS-SEIMC/SAMICEI group, Leon Eva , Camacho Inés Pérez , García David Vinuesa , Pedragosa Jordi Cuquet , Molina Isabel María Reche , Bahamonde-Carrasco Alberto , Rodríguez Carmen Herrero , García Marcos Guzmán , Sánchez-Porto Antonio , Amat Alejandro Smithson , de Lucas Esperanza Merino , Quintero Jesús Canueto 
Published: May 2024

Abstract
Background
Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study.

Methods
Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome.

Results
Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results.

Conclusions
Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.
NCX1/Ca2+ promotes autophagy and decreases bortezomib activity in multiple myeloma through non-canonical NFκB signaling pathway
Authors: Li Tingting , Xiao Pingping , Qiu Dongbiao , Yang Apeng , Chen Qingjiao , Lin Junfang , Liu Yao , Chen Junmin , Zeng Zhiyong 
Published: May 2024

AbstractAlthough bortezomib (BTZ) is the cornerstone of anti-multiple myeloma (MM) therapy, the inevitable primary and secondary drug resistance still seriously affects the prognosis of patients. New treatment strategies are in need. Sodium-calcium exchanger 1 (NCX1) is a calcium-permeable ion transporter on the membrane, and our previous studies showed that low NCX1 confers inferior viability in MM cells and suppressed osteoclast differentiation. However, the effect of NCX1 on BTZ sensitivity of MM and its possible mechanism remain unclear. In this study, we investigated the effect of NCX1 on BTZ sensitivity in MM, focusing on cellular processes of autophagy and cell viability. Our results provide evidence that NCX1 expression correlates with MM disease progression and low NCX1 expression increases BTZ sensitivity. NCX1/Ca2+ triggered autophagic flux through non-canonical NFκB pathway in MM cells, leading to attenuated the sensitivity of BTZ. Knockdown or inhibition of NCX1 could potentiate the anti-MM activity of BTZ in vitro and vivo, and inhibition of autophagy sensitized NCX1-overexpressing MM cells to BTZ. In general, this work implicates NCX1 as a potential therapeutic target in MM with BTZ resistance and provides novel mechanistic insights into its vital role in combating BTZ resistance.
Aberrant activation of TGF-β/ROCK1 enhances stemness during prostatic stromal hyperplasia
Authors: Li Youyou , Li Jiaren , Zhou Liang , Wang Zhenxing , Jin Ling , Cao Jia , Xie Hui , Wang Long 
Published: May 2024

AbstractBenign prostatic hyperplasia (BPH) is a multifactorial disease in which abnormal growth factor activation and embryonic reawakening are considered important factors. Here we demonstrated that the aberrant activation of transforming growth factor β (TGF-β)/Rho kinase 1 (ROCK1) increased the stemness of BPH tissue by recruiting mesenchymal stem cells (MSCs), indicating the important role of embryonic reawakening in BPH. When TGF-β/ROCK1 is abnormally activated, MSCs are recruited and differentiate into fibroblasts/myofibroblasts, leading to prostate stromal hyperplasia. Further research showed that inhibition of ROCK1 activation suppressed MSC migration and their potential for stromal differentiation. Collectively, our findings suggest that abnormal activation of TGF-β/ROCK1 regulates stem cell lineage specificity, and the small molecule inhibitor GSK269962A could target ROCK1 and may be a potential treatment for BPH.
Graphical Abstract
Small molecule inhibitors targeting m6A regulators
Authors: Feng Guotai , Wu Yongya , Hu Yuan , Shuai Wen , Yang Xiao , Li Yong , Ouyang Liang , Wang Guan 
Published: May 2024

AbstractAs the most common form of epigenetic regulation by RNA, N6 methyladenosine (m6A) modification is closely involved in physiological processes, such as growth and development, stem cell renewal and differentiation, and DNA damage response. Meanwhile, its aberrant expression in cancer tissues promotes the development of malignant tumors, as well as plays important roles in proliferation, metastasis, drug resistance, immunity and prognosis. This close association between m6A and cancers has garnered substantial attention in recent years. An increasing number of small molecules have emerged as potential agents to target m6A regulators for cancer treatment. These molecules target the epigenetic level, enabling precise intervention in RNA modifications and efficiently disrupting the survival mechanisms of tumor cells, thus paving the way for novel approaches in cancer treatment. However, there is currently a lack of a comprehensive review on small molecules targeting m6A regulators for anti-tumor. Here, we have comprehensively summarized the classification and functions of m6A regulators, elucidating their interactions with the proliferation, metastasis, drug resistance, and immune responses in common cancers. Furthermore, we have provided a comprehensive overview on the development, mode of action, pharmacology and structure–activity relationships of small molecules targeting m6A regulators. Our aim is to offer insights for subsequent drug design and optimization, while also providing an outlook on future prospects for small molecule development targeting m6A.
The probability of chromatin to be at the nuclear lamina has no systematic effect on its transcription level in fruit flies
Authors: Afanasyev Alexander Y. , Kim Yoonjin , Tolokh Igor S. , Sharakhov Igor V. , Onufriev Alexey V. 
Published: May 2024

Abstract
Background
Multiple studies have demonstrated a negative correlation between gene expression and positioning of genes at the nuclear envelope (NE) lined by nuclear lamina, but the exact relationship remains unclear, especially in light of the highly stochastic, transient nature of the gene association with the NE.

Results
In this paper, we ask whether there is a causal, systematic, genome-wide relationship between the expression levels of the groups of genes in topologically associating domains (TADs) of Drosophila nuclei and the probabilities of TADs to be found at the NE. To investigate the nature of this possible relationship, we combine a coarse-grained dynamic model of the entire Drosophila nucleus with genome-wide gene expression data; we analyze the TAD averaged transcription levels of genes against the probabilities of individual TADs to be in contact with the NE in the control and lamins-depleted nuclei. Our findings demonstrate that, within the statistical error margin, the stochastic positioning of Drosophila melanogaster TADs at the NE does not, by itself, systematically affect the mean level of gene expression in these TADs, while the expected negative correlation is confirmed. The correlation is weak and disappears completely for TADs not containing lamina-associated domains (LADs) or TADs containing LADs, considered separately. Verifiable hypotheses regarding the underlying mechanism for the presence of the correlation without causality are discussed. These include the possibility that the epigenetic marks and affinity to the NE of a TAD are determined by various non-mutually exclusive mechanisms and remain relatively stable during interphase.

Conclusions
At the level of TADs, the probability of chromatin being in contact with the nuclear envelope has no systematic, causal effect on the transcription level in Drosophila. The conclusion is reached by combining model-derived time-evolution of TAD locations within the nucleus with their experimental gene expression levels.
Teaching transposon classification as a means to crowd source the curation of repeat annotation – a tardigrade perspective
Authors: Peona Valentina , Martelossi Jacopo , Almojil Dareen , Bocharkina Julia , Brännström Ioana , Brown Max , Cang Alice , Carrasco-Valenzuela Tomàs , DeVries Jon , Doellman Meredith , Elsner Daniel , Espíndola-Hernández Pamela , Montoya Guillermo Friis , Gaspar Bence , Zagorski Danijela , Hałakuc Paweł , Ivanovska Beti , Laumer Christopher , Lehmann Robert , Boštjančić Ljudevit Luka , Mashoodh Rahia , Mazzoleni Sofia , Mouton Alice , Nilsson Maria Anna , Pei Yifan , Potente Giacomo , Provataris Panagiotis , Pardos-Blas José Ramón , Raut Ravindra , Sbaffi Tomasa , Schwarz Florian , Stapley Jessica , Stevens Lewis , Sultana Nusrat , Symonova Radka , Tahami Mohadeseh S. , Urzì Alice , Yang Heidi , Yusuf Abdullah , Pecoraro Carlo , Suh Alexander 
Published: May 2024

Abstract
Background
The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Moreover, manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences.

Results
Here, we present an example of a crowd-sourcing effort aimed at curating and annotating TE libraries of two non-model species built around a collaborative, peer-reviewed teaching process. Manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd-sourcing efforts could therefore offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries.

Conclusions
The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs in a reasonable time frame. Our crowd-sourcing setting can be used as a teaching reference guide for similar projects: A hidden treasure awaits discovery within non-model organisms.
Single-centre observational study of the safety and efficacy of thoracoscopy under local anaesthesia for the management of thoracic infections
Authors: Fujita Kohei , Saito Zentaro , Ito Takanori , Imakita Takuma , Oi Issei , Kanai Osamu , Yamamoto Yuki , Hata Hiroaki , Sawai Satoru , Tanizawa Kiminobu 
Published: May 2024

Abstract
Objectives
Thoracoscopy under local anaesthesia is widely performed to diagnose malignancies and infectious diseases. However, few reports have described the use of this procedure for diagnosing and treating intrathoracic infections. This study aimed to evaluate the safety and efficacy of thoracoscopy under local anaesthesia for the management of intrathoracic infections.

Results
Data from patients who underwent thoracoscopy procedures performed by chest physicians under local anaesthesia at our hospital between January 2018 and December 2023 were retrospectively reviewed. We analysed their demographic factors, reasons for the examinations, diseases targeted, examination lengths, anaesthetic methods used, diagnostic and treatment success rates, as well as any adverse events. Thirty patients were included. Of these, 12 (40%) had thoracoscopies to diagnose infections, and 18 (60%) had them to treat pyothorax. In terms of diagnosing pleurisy, the causative microorganism of origin was identified via thoracoscopy in only three of 12 (25.0%) patients. For diagnosing pyothorax, the causative microorganism was identified in 7 of 18 (38.9%) patients. Methicillin-resistant Staphylococcus aureus was the most common causative microorganism identified. The treatment success rates were very high, ranging between 94.4 and 100%, whereas the identification rate of the causative microorganisms behind infections was low, ranging between 25.0 and 38.9%. The most frequent adverse events included perioperative hypoxaemia and pain. There were two (6.7%) serious adverse events of grade ≥ 3, but none resulted in death.

Conclusions
The efficacy of managing intrathoracic infections through thoracoscopy under local anaesthesia is commendable. Nonetheless, the diagnostic accuracy of the procedure, regarding the precise identification of the causative microorganisms responsible for intrathoracic infections, persists at a notably low level, presenting a substantial clinical hurdle.
Sirenomelia or mermaid syndrome with a cleft lip in a Tanzanian newborn: a case report
Authors: Wilfred Zakaria Ismail , Magitta Ng’weina Francis 
Published: May 2024

Abstract
Background
Sirenomelia or sirenomelia sequence, also known as mermaid syndrome, is a rare congenital anomaly involving the caudal region of the body. The syndrome is characterized by partial or complete fusion of lower extremities, renal agenesis, absent urinary tract, ambiguous external genitalia, imperforate anus, and single umbilical artery. Sirenomelia is often associated with several visceral congenital malformations, rendering it invariably incompatible with extrauterine life.

Case presentation
We present the case of 22-year-old Black African woman who delivered a term newborn by caesarean section at a gestation age of 37 weeks due to obstructed labor with fetal distress. The newborn was a fresh stillbirth weighing 2100 g and had fusion of the lower extremities, a single upper limb, ambiguous genitalia, imperforate anus, and a cleft lip. The mother had made only two prenatal visits, at which she was found to be normotensive and normoglycemic. She was not screened for routine fetomaternal infections and missed supplementation for folic acid during the critical first trimester. She did not undergo any obstetric ultrasonography. The parents of the newborn were not close relatives and there was no family history of consanguinity. Further genetic testing was not performed due to lack of laboratory capacity, and post mortem examination was not permitted due to cultural taboo and restrictions relating to handling of deceased newborns.

Conclusion
Sirenomelia is a rare congenital malformation with very poor prognosis. Specific interventions during pre-conception and early prenatal care are critical in the prevention of specific congenital anomalies. Early obstetric ultrasonography is invaluable for diagnosis of sirenomelia as well as counseling for possible termination of pregnancy.