bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring autochthonous lung tumors induced by somatic CRISPR gene editing in mice using a secreted luciferase
Authors: Merle Nastasja , Elmshäuser Sabrina , Strassheimer Florian , Wanzel Michael , König Alexander M. , Funk Julianne , Neumann Michelle , Kochhan Katharina , Helmprobst Frederik , Pagenstecher Axel , Nist Andrea , Mernberger Marco , Schneider André , Braun Thomas , Borggrefe Tilman , Savai Rajkumar , Timofeev Oleg , Stiewe Thorsten 
Published: October 2022

Abstract
Background
In vivo gene editing of somatic cells with CRISPR nucleases has facilitated the generation of autochthonous mouse tumors, which are initiated by genetic alterations relevant to the human disease and progress along a natural timeline as in patients. However, the long and variable, orthotopic tumor growth in inner organs requires sophisticated, time-consuming and resource-intensive imaging for longitudinal disease monitoring and impedes the use of autochthonous tumor models for preclinical studies.

Methods
To facilitate a more widespread use, we have generated a reporter mouse that expresses a Cre-inducible luciferase from Gaussia princeps (GLuc), which is secreted by cells in an energy-consuming process and can be measured quantitatively in the blood as a marker for the viable tumor load. In addition, we have developed a flexible, complementary toolkit to rapidly assemble recombinant adenoviruses (AVs) for delivering Cre recombinase together with CRISPR nucleases targeting cancer driver genes.

Results
We demonstrate that intratracheal infection of GLuc reporter mice with CRISPR-AVs efficiently induces lung tumors driven by mutations in the targeted cancer genes and simultaneously activates the GLuc transgene, resulting in GLuc secretion into the blood by the growing tumor. GLuc blood levels are easily and robustly quantified in small-volume blood samples with inexpensive equipment, enable tumor detection already several months before the humane study endpoint and precisely mirror the kinetics of tumor development specified by the inducing gene combination.

Conclusions
Our study establishes blood-based GLuc monitoring as an inexpensive, rapid, high-throughput and animal-friendly method to longitudinally monitor autochthonous tumor growth in preclinical studies.
Establishment and validation of a postoperative predictive model for patients with colorectal mucinous adenocarcinoma
Authors: Wang Pengchao , Song Qingyu , Lu Ming , Xia Qingcheng , Wang Zijun , Zhao Qinghong , Ma Xiang 
Published: October 2022

Abstract
Background
The aim of this study was to develop comprehensive and effective nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) rates in patients with colorectal mucinous adenocarcinoma (CRMA).

Methods
A total of 4711 CRMA patients who underwent radical surgery between 2010 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database were collected and randomized into development (n=3299) and validation (n=1412) cohorts at a ratio of 7:3 for model development and validation. OS and CSS nomograms were developed using the prognostic factors from the development cohort after multivariable Cox regression analysis. The performance of the nomograms was evaluated using Harrell’s concordance index (C-index), calibration diagrams, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA).

Results
The study included 4711 patients. Multivariate Cox regression analysis demonstrated that age, tumor size, grade, pT stage, pN stage, M stage, carcinoembryonic antigen, perineural invasion, tumor deposits, regional nodes examined, and chemotherapy were correlated with OS and CSS. Marital status was independently related to OS. In the development and validation cohorts, the C-index of OS was 0.766 and 0.744, respectively, and the C-index of CSS was 0.826 and 0.809, respectively. Calibration curves and ROC curves showed predictive accuracy. DCA showed that the nomograms had excellent potency over the 8th edition of the TNM staging system with higher clinical net benefits. Significant differences in OS and CSS were observed among low-, medium-, and high-risk groups.

Conclusions
Nomograms were developed for the first time to predict personalized 1-, 3-, and 5-year OS and CSS in CRMA postoperative patients. External and internal validation confirmed the excellent discrimination and calibration ability of the nomograms. The nomograms can help clinicians design personalized treatment strategies and assist with clinical decisions.
Prevalence of reproductive tract infections among women preparing to conceive in Chongqing, China: trends and risk factors
Authors: Liu Jun , Zeng Mengyao , Yang Liu , Mao Yanyan , He Yang , Li Min , Chen Qing , Zhou Weijin , Chen Liang , Zhu Qianxi 
Published: October 2022

AbstractBackgroundReproductive tract infection has become a major public health issue all over the world for its high and growing prevalence. It can cause adverse pregnancy outcomes in pregnant women and their foetuses. This study aimed to investigate the trends and risk factors of the prevalence of reproductive tract infections among women who prepared to conceive in the Chongqing Municipality (China) from 2012 to 2016.MethodsA multi-center cross-sectional study was conducted between January 2012 and December 2016. Women aged 20–49 years who intended to get pregnant were recruited for this study. All participants underwent preconception examination, which included testing forNeisseria gonorrhoeae,Chlamydia trachomatis,Trichomonas vaginalis, syphilis, bacterial vaginosis and candidiasis according to the national diagnostic standard. A total of 439,372 women with testing results for all six types of reproductive tract infections were included in our final analyses. Logistic regression and factor analysis were used to determine the possible sociodemographic factors associated with prevalence trends.ResultsIn our study, the overall positive rate of RTIs among the 439,372 women of reproductive age was 5.03%. Candidiasis was the most common infection in our population (2.47%), followed by bacterial vaginosis (1.28%), syphilis (0.73%),T. vaginalis(0.49%),C. trachomatis(0.20%) andN. gonorrhoeae(0.06%). The prevalence of reproductive tract infections was highest among women aged 35 years and above, with a primary or lower education level, history of pregnancy, delivery, induced abortion, or spontaneous abortion. From 2012 to 2016, the trend of the overall prevalence of reproductive tract infections was V-shaped, decreasing steadily from 2012 to 2015, with a slight rise in 2016. Our results suggest that the distribution change of age, education level, gravidity, parity, and history of induced abortion influenced this trend.ConclusionSince the number of high-risk women who intend to become pregnant is growing in the Chongqing Municipality, pre-conception positive preventions including health education, regular screening, and timely treatment of reproductive tract infections are needed to prevent the impact of reproductive tract infections on maternal health and infant safety.
Clinical and molecular characterization of 1q43q44 deletion and corpus callosum malformations: 2 new cases and literature review
Authors: Khadija Bochra , Rjiba Khouloud , Dimassi Sarra , Dahleb Wafa , Kammoun Molka , Hannechi Hanen , Miladi Najoua , Gouider-khouja Neziha , Saad Ali , Mougou-Zerelli Soumaya 
Published: October 2022

Abstract
Background
Corpus callosum malformations (CCM) represent one of the most common congenital cerebral malformations with a prevalence of around one for 4000 births. There have been at least 230 reports in the literature concerning 1q43q44 deletions of varying sizes discovered using chromosomal microarrays. This disorder is distinguished by global developmental delay, seizures, hypotonia, corpus callosum defects, and significant craniofacial dysmorphism. In this study, we present a molecular cytogenetic analysis of 2 Tunisian patients with corpus callosum malformations. Patient 1 was a boy of 3 years old who presented psychomotor retardation, microcephaly, behavioral problems, interventricular septal defect, moderate pulmonary stenosis, hypospadias, and total CCA associated with delayed encephalic myelination. Patient 2 was a boy of 9 months. He presented a facial dysmorphia, a psychomotor retardation, an axial hypotonia, a quadri pyramidal syndrome, a micropenis, and HCC associated with decreased volume of the periventricular white matter. Both the array comparative genomic hybridization and fluorescence in situ hybridization techniques were used.

Results
Array CGH analysis reveals that patient 1 had the greater deletion size (11,7 Mb) at 1q43. The same region harbors a 2,7 Mb deletion in patient 2. Here, we notice that the larger the deletion, the more genes are likely to be involved, and the more severe the phenotype is likely to be. In both patients, the commonly deleted region includes six genes: PLD5, AKT3, ZNF238, HNRNPU, SDCCAG8 and CEP170. Based on the role of the ZNF238 gene in neuronal proliferation, migration, and cortex development, we hypothesized that the common deletion of ZNF238 in both patients seems to be the most responsible for corpus callosum malformations. Its absence may directly cause CCM. In addition, due to their high expression in the brain, PLD5 and FMN2 could modulate in the CCM phenotype.

Conclusion
Our findings support and improve the complex genotype–phenotype correlations previously reported in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of several genes related to this pathology.
H3K18 lactylation marks tissue-specific active enhancers
Authors: Galle Eva , Wong Chee-Wai , Ghosh Adhideb , Desgeorges Thibaut , Melrose Kate , Hinte Laura C. , Castellano-Castillo Daniel , Engl Magdalena , de Sousa Joao Agostinho , Ruiz-Ojeda Francisco Javier , De Bock Katrien , Ruiz Jonatan R. , von Meyenn Ferdinand 
Published: October 2022

Abstract
Background
Histone lactylation has been recently described as a novel histone post-translational modification linking cellular metabolism to epigenetic regulation.

Results
Given the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG island-containing promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue.

Conclusions
Overall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers.
Engineering Yarrowia lipolytica for the sustainable production of β-farnesene from waste oil feedstock
Authors: Liu Yinghang , Zhang Jin , Li Qingbin , Wang Zhaoxuan , Cui Zhiyong , Su Tianyuan , Lu Xuemei , Qi Qingsheng , Hou Jin 
Published: October 2022

Abstract
Background
β-Farnesene is a sesquiterpene with versatile industrial applications. The production of β-farnesene from waste lipid feedstock is an attractive method for sustainable production and recycling waste oil. Yarrowia lipolytica is an unconventional oleaginous yeast, which can use lipid feedstock and has great potential to synthesize acetyl-CoA-derived chemicals.

Results
In this study, we engineered Y. lipolytica to produce β-farnesene from lipid feedstock. To direct the flux of acetyl-CoA, which is generated from lipid β-oxidation, to β-farnesene synthesis, the mevalonate synthesis pathway was compartmentalized into peroxisomes. β-Farnesene production was then engineered by the protein engineering of β-farnesene synthase and pathway engineering. The regulation of lipid metabolism by enhancing β-oxidation and eliminating intracellular lipid synthesis was further performed to improve the β-farnesene synthesis. As a result, the final β-farnesene production with bio-engineering reached 35.2 g/L and 31.9 g/L using oleic acid and waste cooking oil, respectively, which are the highest β-farnesene titers reported in Y. lipolytica.

Conclusions
This study demonstrates that engineered Y. lipolytica could realize the sustainable production of value-added acetyl-CoA-derived chemicals from waste lipid feedstock.
Capparis spinosa improves non-alcoholic steatohepatitis through down-regulating SREBP-1c and a PPARα-independent pathway in high-fat diet-fed rats
Authors: Akbari Rasoul , Yaghooti Hamid , Jalali Mohammad Taha , Khorsandi Laya Sadat , Mohammadtaghvaei Narges 
Published: October 2022

Abstract
Objective
Non-alcoholic steatohepatitis (NASH) has become a global medical problem. Currently, there is no approved pharmacologic treatment for this condition. Previous studies have suggested that in the pathogenesis of this disease, regulatory pathways associated with de novo lipogenesis and β-oxidation pathways genes are misregulated. Capparis spinosa (CS) belongs to the family of Capparidaceae and is a traditional plant used to treat various diseases, particularly dyslipidemia. The compounds and extracts of this plant in In vivo and in vitro studies resulted in a reduction in lipid profiles and glucose. However, the mechanism of these effects remains unknown. This study aimed to evaluate the effects of (CS) fruit extract on NASH compared to fenofibrate and explored the related molecular mechanism.

Results
In the rats (n = 40) model of NASH, biochemical and histopathological examinations showed that liver steatosis, inflammation, and hepatic fibrosis were markedly attenuated in response to CS and fenofibrate interventions. At the molecular level, CS treatment down-regulated sterol regulatory element-binding protein-1c (SREBP-1c) (p < 0.001), acetyl-CoA carboxylase (ACC) (p < 0.001), and up-regulated Carnitine palmitoyltransferase I (CPT1) expression (p < 0.001). In conclusion, CS has favorable therapeutic effects for NASH, which was associated with ameliorating steatosis and fibrosis via regulation of the DNL and β-oxidation pathway genes.

Graphical Abstract
Effects of Moringa oleifera on working memory: an experimental study with memory-impaired Wistar rats tested in radial arm maze
Authors: Afrin Sadia , Hossain Ahmed , Begum Shelina 
Published: October 2022

Abstract
Objective
Memory impairment is a serious problem that has a significant negative impact on survival and quality of life. When used for a long time, drugs used to treat memory loss become less effective and have more side effects, making therapy more difficult. Different medicinal plants are now being highlighted because of their valuable applications and low risk of adverse effects. Moringa oleifera is one of these plants that has gained much attention due to its diverse biological functions. The study aimed to determine the effects of Moringa oleifera on working memory in memory-impaired Wistar rats.

Results
For this experimental study, 30 male Wistar rats having 150–250 g bodyweight were divided equally into three groups: Group-I/normal memory group (treated with oral normal saline 5 ml/kg body weight), Group-II/memory-impaired group (induced by intraperitoneal ketamine 15 mg/kg body weight), and Group-III/experimental group (treated with oral Moringa oleifera 200 mg/kg bodyweight and intraperitoneal ketamine 15 mg/kg body weight). The experimental group showed significantly fewer working memory errors than the memory-impaired group. The experimental group also provides the lowest variability of WMEs among groups. Thus, the study concludes that M. oleifera can prevent ketamine-induced memory impairment in Wistar rats.
Enhanced fear limits behavioral flexibility in Shank2-deficient mice
Authors: Yun Miru , Kim Eunjoon , Jung Min Whan 
Published: October 2022

Abstract
Background
A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD.

Methods
We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6 µl) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice.

Results
Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards.

Limitations
We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated.

Conclusions
Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD.
Irony detection in patients with borderline personality disorder: an experimental study examining schizotypal traits, response biases and empathy
Authors: Felsenheimer Anne Katrin , Kieckhäfer Carolin , Rapp Alexander Michael 
Published: October 2022

AbstractBackgroundIn verbal irony we often convey meanings that oppose the literal words. To look behind these words, we need to integrate perspectives of ourselves, others, and their beliefs about us. Although patients with borderline personality disorder (BPD) experience problems in social cognition and schizotypal symptoms, research on irony comprehension mainly focused on the schizophrenic spectrum. Accounting for possible negative biases in BPD, the current study examined the detection of praising and critical irony in a text messaging interface.MethodsThe cross-sectional study included 30 patients and 30 matched controls, who completed measures of cognitive and affective empathy (Interpersonal Reactivity Index, IRI), schizotypal (Schizotypal Personality Questionnaire; SPQ), and borderline symptoms (Borderline Symptom List; BSL-23) and the irony detection task. The irony task contained critical and praising remarks embedded in text messages. Asking for literality (ironic vs. literal) and intention ratings (critical to praising) of the stimuli, it allowed to analyze the sensitivity of literality detection as well as implicit and explicit response biases in a signal detection framework.ResultsBorderline symptoms explained lower sensitivity for the detection of literal and ironic statements across groups. Whereas HC showed a negativity bias when implicitly asked about the literalness of the statement, patients with BPD perceived praising utterances as less praising when explicitly asked about their perceived intention. Neither empathy nor schizotypy explained outcomes beyond borderline symptoms.ConclusionsThis was the first study to show lower detection of verbal irony in patients with BPD. While patients were less biased when asked about the literality of a statement, they perceived praising remarks as less positive on explicit measurements. The results highlight the importance of congruent, transparent communication in promoting epistemic trust in individuals with BPD.
Long-term efficacy with deep brain stimulation of the globus pallidus internus in cervical dystonia: a retrospective monocentric study
Authors: Jacksch Clemens , Zeuner Kirsten E. , Helmers Ann-Kristin , Witt Karsten , Deuschl Günther , Paschen Steffen 
Published: October 2022

Abstract
Background
Cervical dystonia (CD) is characterized by involuntary contractions of the cervical muscles. Data on long-term effectiveness of deep brain stimulation (DBS) are rare. The aim of this study was to evaluate the longitudinal ten years treatment efficacy of DBS in the globus pallidus internus (GPI).

Methods
A retrospective single-center data analysis was performed on patients with idiopathic CD, who were treated with GPI DBS for at least 10 years. TWSTR severity score and individual sub-items were compared between pre and post DBS surgery (n = 15) over time.

Results
There was a significant and persistent positive effect regarding the severity of TWSTRS between the conditions immediately before and 1, 5, and 10 years after establishment of GPI DBS (mean difference: 6.6–7 ± 1.6). Patients with increasing CD complexity showed a poorer response to established treatment forms, such as injection of botulinum toxin and were thus DBS candidates. Especially a predominant torticollis was significantly improved by DBS.

Conclusion
GPI DBS is an effective procedure especially in severely affected patients with a positive 10-year outcome. It should be considered in more complex CD-forms or predominant torticollis.
Hypnotherapy and therapeutic suggestion: bridging the gap between evidence and utility
Authors: Orewa Henry , Udo Itoro 
Published: October 2022

SUMMARYThe use of hypnotherapy in psychiatry has been controversial. However, evidence presented by Chan and colleagues shows that it is beneficial to the promotion of good mental health and well-being, specifically being applicable in the management of mental disorders. But what does this mean for practice? This commentary looks at what we agree and disagree with, what we opine is missing from the article and what now needs to happen. Patients should be able to access hypnotherapy or hypnosis routinely on the National Health Service. Since it works, who may it work for and how may we make this available to those who could benefit from it?