bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neomorphic DNA-binding enables tumor-specific therapeutic gene expression in fusion-addicted childhood sarcoma
Authors: Hölting Tilman L. B. , Cidre-Aranaz Florencia , Matzek Dana , Popper Bastian , Jacobi Severin J. , Funk Cornelius M. , Geyer Florian H. , Li Jing , Piseddu Ignazio , Cadilha Bruno L. , Ledderose Stephan , Zwilling Jennifer , Ohmura Shunya , Anz David , Künkele Annette , Klauschen Frederick , Grünewald Thomas G. P. , Knott Maximilian M. L. 
Published: October 2022

AbstractChimeric fusion transcription factors are oncogenic hallmarks of several devastating cancer entities including pediatric sarcomas, such as Ewing sarcoma (EwS) and alveolar rhabdomyosarcoma (ARMS). Despite their exquisite specificity, these driver oncogenes have been considered largely undruggable due to their lack of enzymatic activity.Here, we show in the EwS model that – capitalizing on neomorphic DNA-binding preferences – the addiction to the respective fusion transcription factor EWSR1-FLI1 can be leveraged to express therapeutic genes.We genetically engineered a de novo enhancer-based, synthetic and highly potent expression cassette that can elicit EWSR1-FLI1-dependent expression of a therapeutic payload as evidenced by episomal and CRISPR-edited genomic reporter assays. Combining in silico screens and immunohistochemistry, we identified GPR64 as a highly specific cell surface antigen for targeted transduction strategies in EwS. Functional experiments demonstrated that anti-GPR64-pseudotyped lentivirus harboring our expression cassette can specifically transduce EwS cells to promote the expression of viral thymidine kinase sensitizing EwS for treatment to otherwise relatively non-toxic (Val)ganciclovir and leading to strong anti-tumorigenic, but no adverse effects in vivo. Further, we prove that similar vector designs can be applied in PAX3-FOXO1-driven ARMS, and to express immunomodulatory cytokines, such as IL-15 and XCL1, in tumor entities typically considered to be immunologically ‘cold’.Collectively, these results generated in pediatric sarcomas indicate that exploiting, rather than suppressing, the neomorphic functions of chimeric transcription factors may open inroads to innovative and personalized therapies, and that our highly versatile approach may be translatable to other cancers addicted to oncogenic transcription factors with unique DNA-binding properties.
Interplay of the transcription factor MRTF-A and matrix stiffness controls mammary acinar structure and protrusion formation
Authors: Melcher Marie-Luise , Block Ines , Kropf Karolin , Singh Anurag Kumar , Posern Guido 
Published: October 2022

Abstract
Background
Ongoing differentiation processes characterize the mammary gland during sexual development and reproduction. In contrast, defective remodelling is assumed to be causal for breast tumorigenesis. We have shown recently that the myocardin-related transcription factor A (MRTF-A) is essential for forming regular hollow acinar structures. Moreover, MRTF-A activity is known to depend on the biochemical and physical properties of the surrounding extracellular matrix. In this study we analysed the mutual interaction of different matrix stiffnesses and MRTF-A activities on formation and maintenance of mammary acini.

Methods
Human MCF10A acini and primary mature organoids isolated from murine mammary glands were cultivated in 3D on soft and stiff matrices (200–4000 Pa) in conjunction with the Rho/MRTF/SRF pathway inhibitor CCG-203971 and genetic activation of MRTF-A.

Results
Three-dimensional growth on stiff collagen matrices (> 3000 Pa) was accompanied by increased MRTF-A activity and formation of invasive protrusions in acini cultures of human mammary MCF10A cells. Differential coating and synthetic hydrogels indicated that protrusion formation was attributable to stiffness but not the biochemical constitution of the matrix. Stiffness-induced protrusion formation was also observed in preformed acini isolated from murine mammary glands. Acinar outgrowth in both the MCF10A acini and the primary organoids was partially reverted by treatment with the Rho/MRTF/SRF pathway inhibitor CCG-203971. However, genetic activation of MRTF-A in the mature primary acini also reduced protrusion formation on stiff matrices, whilst it strongly promoted luminal filling matrix-independently.

Conclusion
Our results suggest an intricate crosstalk between matrix stiffness and MRTF-A, whose activity is required for protrusion formation and sufficient for luminal filling of mammary acini.
Quantitative measurement of resistance force and subsequent attenuation during passive isokinetic extension of the wrist in patients with mild to moderate spasticity after stroke
Authors: Kawamura Kentaro , Etoh Seiji , Noma Tomokazu , Hayashi Ryota , Jonoshita Yuiko , Natsume Keisuke , Niidome Seiichi , Yu Yong , Shimodozono Megumi 
Published: October 2022

Abstract
Background
Spasticity is evaluated by measuring the increased resistance to passive movement, primarily by manual methods. Few options are available to measure spasticity in the wrist more objectively. Furthermore, no studies have investigated the force attenuation following increased resistance. The aim of this study was to conduct a safe quantitative evaluation of wrist passive extension stiffness in stroke survivors with mild to moderate spastic paresis using a custom motor-controlled device. Furthermore, we wanted to clarify whether the changes in the measured values could quantitatively reflect the spastic state of the flexor muscles involved in the wrist stiffness of the patients.

Materials and methods
Resistance forces were measured in 17 patients during repetitive passive extension of the wrist at velocities of 30, 60, and 90 deg/s. The Modified Ashworth Scale (MAS) in the wrist and finger flexors was also assessed by two skilled therapists and their scores were averaged (i.e., average MAS) for analysis. Of the fluctuation of resistance, we focused on the damping just after the peak forces and used these for our analysis. A repeated measures analysis of variance was conducted to assess velocity-dependence. Correlations between MAS and damping parameters were analyzed using Spearman’s rank correlation.

Results
The damping force and normalized value calculated from damping part showed significant velocity-dependent increases.
There were significant correlations (ρ = 0.53–0.56) between average MAS for wrist and the normalized value of the damping part at 90 deg/s. The correlations became stronger at 60 deg/s and 90 deg/s when the MAS for finger flexors was added to that for wrist flexors (ρ = 0.65–0.68).

Conclusions
This custom-made isokinetic device could quantitatively evaluate spastic changes in the wrist and finger flexors simultaneously by focusing on the damping part, which may reflect the decrease in resistance we perceive when manually assessing wrist spasticity using MAS.
Trial registration UMIN Clinical Trial Registry, as UMIN000030672, on July 4, 2018
Laparoscopic versus open emergent colectomy for ischemic colitis: a propensity score-matched comparison
Authors: Chen Yi-Chang , Tsai Yuan-Yao , Chang Sheng-Chi , Chen Hung-Chang , Ke Tao-Wei , Fingerhut Abe , Chen William Tzu-Liang 
Published: October 2022

Abstract
Introduction
Laparoscopic colectomy is rarely performed for ischemic colitis. The aim of this propensity score-matched study was to compare preoperative characteristics, intraoperative details and short-term outcomes for emergent laparoscopic colectomy versus the traditional open approach for patients with ischemic colitis.

Methods
Retrospective review of 96 patients who underwent emergent colectomy for ischemic colitis between January 2011 and December 2020 (39 via laparoscopy, 57 via laparotomy) was performed. We compared short-term outcomes after using a one-to-one ratio and nearest-neighbor propensity score matching to obtain similar preoperative and intraoperative parameters in each group.

Results
Patients in the open group experienced more surgical site complications (52.6% vs. 23.0%, p = 0.004), more intra-abdominal abscesses (47.3% vs. 17.9%, p = 0.003), longer need for ventilator support (20 days vs. 0 days, p < 0.001), more major complications (77.2% vs. 43.5%, p = 0.001), higher mortality (49.1% vs. 20.5%, p = 0.004), and longer hospital stay (32 days vs. 19 days, p = 0.001). After propensity score matching (31 patients in each group), patients undergoing open (vs. laparoscopy) had more surgical site complications (45.1% vs. 19.4%, p = 0.030) and required longer ventilator support (14 vs. 3 days, p = 0.039). After multivariate analysis, Charlson Comorbidity Index (p = 0.024), APACHE II score (p = 0.001), and Favier’s classification (p = 0.023) were independent predictors of mortality.

Conclusions
Laparoscopic emergent colectomy for ischemic colitis is feasible and is associated with fewer surgical site complications and better respiratory function, compared to the open approach.
Metabolic engineering of Escherichia coli BW25113 for the production of 5-Aminolevulinic Acid based on CRISPR/Cas9 mediated gene knockout and metabolic pathway modification
Authors: Ye Changchuan , Yang Yuting , Chen Xi , Yang Lijie , Hua Xia , Yang Mengjie , Zeng Xiangfang , Qiao Shiyan 
Published: October 2022

Abstract
Background
5-Aminolevulinic acid (ALA) recently received much attention due to its potential application in many fields. In this study, an ALA production strain of Escherichia coli was constructed by rational metabolic engineering and stepwise improvement based on known regulatory and metabolic information and CRISPR/Cas9 mediated gene knockout.

Results
A metabolic strategy to produce ALA directly from glucose in this recombinant E. coli via the C5 pathway was applied herein. The rational metabolic engineering by gene knockouts significantly improved ALA production from 662.3 to 1601.7 mg/L. In addition, we managed to synergistically produce ALA via the C4 pathway in recombinant strain. The expression of a modified hemA gene, encoding an ALA synthase from Rhodobacter sphaeroides, improved ALA production from 1601.7 to 2099.7 mg/L. After 24 h cultivation, a yield of 0.210 g ALA per g glucose was achieved by constructed E. coli D5:FYABD-RSA.

Conclusion
Our study revealed that an industrially competitive strain can be efficiently developed by metabolic engineering based on combined rational modification and optimization of gene expression.
Experimentally designed electrochemical sensor for therapeutic drug monitoring of Ondansetron co-administered with chemotherapeutic drugs
Authors: Abdel Rahman Mona A. , Atty Shimaa A. , El-Mosallamy Sally S. , Elghobashy Mohamed R. , Zaazaa Hala E. , Saad Ahmed S. 
Published: October 2022

AbstractThe experimental design extracts valuable information about the main effects and interactions from the least number of experiments. The current work constructs a solid-state sensor for selective assay of Ondansetron (OND) in pharmaceutical dosage form and plasma samples. During optimization, the Design Expert®statistical package constructed a custom design of 15 sensors with different recipes. We fed the software with the experimentally observed performance parameters for each sensor (slope, LOQ, correlation coefficient, and selectivity coefficient for sodium ions). The computer software analyzed the results to construct a prediction model for each response. The desirability function was adjusted to optimize the Nernstian slope, minimize the LOQ and selectivity coefficients, and maximize the correlation coefficient (r). The practical responses of the optimized sensor were close to those predicted by the model (slope = 60.23 mV/decade slope, LOQ = 9.09 × 10–6 M, r = 0.999, sodium selectivity coefficient = 1.09 × 10−3). The sensor successfully recovered OND spiked to tablets and human plasma samples with mean percentage recoveries of 100.01 ± 1.082 and 98.26 ± 2.227, respectively. Results were statistically comparable to those obtained by the reference chromatographic method. The validated potentiometric method can be used for fast and direct therapeutic drug monitoring of OND co-administered with chemotherapeutic drugs in plasma samples.
Nationwide molecular survey of Dirofilaria immitis and Dirofilaria repens in companion dogs and cats, United States of America
Authors: Smith Rachel , Murillo Daniel Felipe Barrantes , Chenoweth Kelly , Barua Subarna , Kelly Patrick John , Starkey Lindsay , Blagburn Byron , Wood Theresa , Wang Chengming 
Published: October 2022

Abstract
Background
Heartworms, Dirofilaria immitis, are known to be widespread in dogs and cats in the USA, but there have been no country-wide prevalence studies performed to date. There have also been no large-scale studies to determine whether the closely related species, Dirofilaria repens, occurs in the USA.

Methods
To provide this large-scale data, we examined whole blood samples (n = 2334) submitted from around the USA to the Molecular Diagnostic Laboratory at Auburn University between 2016 and 2022. Quantitative PCRs for D. immitis (targeting 16S rRNA) and D. repens (targeting cytochrome c oxidase subunit 1 gene) were performed to determine the presence of Dirofilaria DNA. DNA sequencing was performed to confirm the results.

Results
Dirofilaria immitis DNA was found in 6.3% (68/1080) of the dogs from 17/39 states, and 0.3% (4/1254) of the cats from 4/42 states. None of the dogs or cats were positive for D. repens. The average 16S rRNA copy number of D. immitis in the dogs was 1,809,604 in 200 µl whole blood, while only a single copy was found in each of the four D. immitis-positive cats. The prevalence of D. immitis in dogs of different ages, sexes, and breeds did not differ significantly, but the prevalence in Southern states (7.5%, 60/803) was significantly higher than in the Western (1.7%, 1/58), Midwest (3.3%, 4/120), and Northeastern states (3.1%, 3/98) (P < 0.05). Dogs positive for D. immitis were identified in each study year (2016: 4.2%, 2/48; 2017: 9.8%, 4/41; 2018: 5.1%, 8/156; 2019: 4.9%, 15/306; 2020: 9.8%, 26/265; 2021: 4.9%, 13/264). Interestingly, dogs infected with Hepatozoon spp. (11.8%, 37/313) were significantly more likely to also be positive for D. immitis than dogs without evidence of Hepatozoon infection (3.9%, 30/760) (P < 0.0001).

Conclusions
To our knowledge, this is the first nationwide molecular survey of Dirofilaria spp. in dogs and cats in the USA, and the largest molecular survey of canine and feline dirofilariosis worldwide. Further studies are warranted to combine PCR with standard heartworm diagnostics to better understand the prevalence of Dirofilaria spp. and aid in determining the risks posed to dogs and cats in the USA.

Graphical Abstract
CTpathway: a CrossTalk-based pathway enrichment analysis method for cancer research
Authors: Liu Haizhou , Yuan Mengqin , Mitra Ramkrishna , Zhou Xu , Long Min , Lei Wanyue , Zhou Shunheng , Huang Yu-e , Hou Fei , Eischen Christine M. , Jiang Wei 
Published: October 2022

Abstract
Background
Pathway enrichment analysis (PEA) is a common method for exploring functions of hundreds of genes and identifying disease-risk pathways. Moreover, different pathways exert their functions through crosstalk. However, existing PEA methods do not sufficiently integrate essential pathway features, including pathway crosstalk, molecular interactions, and network topologies, resulting in many risk pathways that remain uninvestigated.

Methods
To overcome these limitations, we develop a new crosstalk-based PEA method, CTpathway, based on a global pathway crosstalk map (GPCM) with >440,000 edges by combing pathways from eight resources, transcription factor-gene regulations, and large-scale protein-protein interactions. Integrating gene differential expression and crosstalk effects in GPCM, we assign a risk score to genes in the GPCM and identify risk pathways enriched with the risk genes.

Results
Analysis of >8300 expression profiles covering ten cancer tissues and blood samples indicates that CTpathway outperforms the current state-of-the-art methods in identifying risk pathways with higher accuracy, reproducibility, and speed. CTpathway recapitulates known risk pathways and exclusively identifies several previously unreported critical pathways for individual cancer types. CTpathway also outperforms other methods in identifying risk pathways across all cancer stages, including early-stage cancer with a small number of differentially expressed genes. Moreover, the robust design of CTpathway enables researchers to analyze both bulk and single-cell RNA-seq profiles to predict both cancer tissue and cell type-specific risk pathways with higher accuracy.

Conclusions
Collectively, CTpathway is a fast, accurate, and stable pathway enrichment analysis method for cancer research that can be used to identify cancer risk pathways. The CTpathway interactive web server can be accessed here http://www.jianglab.cn/CTpathway/. The stand-alone program can be accessed here https://github.com/Bioccjw/CTpathway.
The relationship between core muscle endurance and functional movement screen scores in females with lumbar hyperlordosis: a cross-sectional study
Authors: Fallahasady Eiva , Rahmanloo Nafise , Seidi Foad , Rajabi Reza , Bayattork Mohammad 
Published: October 2022

Abstract
Background
Core muscle endurance is essential for proper movement and lower extremity injury prevention. In addition, the Functional Movement Screen (FMS) score is a tool to assess body movement patterns to predict the risk of injury. Although various researches have investigated the relationship between the core muscle endurance and the FMS score, no study has ever assessed the effect of postural deformity on the FMS score. This study investigates the relationship between core muscle endurance and FMS scores in females with lumbar hyperlordosis.

Methods
42 healthy females aged 24.03 ± 4.4 years with hyperlordosis ( > = 45/66 degrees) participated in this study. Core muscle endurance was assessed by the McGill stability test. Correlations were evaluated between the FMS score, McGill test, and lordosis angle using spearman correlation coefficients (p ≤ 0.05).

Results
Most individual FMS scores were not correlated with the McGill test except stability trunk push up. Also, lordosis angle was not correlated with the FMS composite score (r=-0.077; p = 0.631), while it was negatively correlated with the McGill test (r=-0.650; p = 0.000).

Conclusion
The lack of correlation between the FMS score and the McGill test implies that one’s level of core endurance may not influence their functional movement patterns. In contrast, the lumbar lordosis angle might impact one’s core muscle endurance but not their functional movement patterns.
Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease?
Authors: Rota Silvia , Urso Daniele , van Wamelen Daniel J. , Leta Valentina , Boura Iro , Odin Per , Espay Alberto J. , Jenner Peter , Chaudhuri K. Ray 
Published: October 2022

AbstractContinuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson’s disease (PD) to control motor and non-motor fluctuations (‘OFF’ periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD. All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD. A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of ‘OFF’ periods. However, data suggest that despite their efficacy in reducing the number and duration of ‘OFF’ periods, these strategies still do not prevent ‘OFF’ periods in the middle to late stages of PD, thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation. Why these emergent ‘OFF’ periods still occur is unknown. In this review, we analyse the potential reasons for their persistence. The contribution of drug- and device-related involvement, and the problems related to site-specific drug delivery are analysed. We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent ‘OFF’ periods unresponsive to dopaminergic therapy delivered via CDD.
Clinical research diagnostic criteria for bipolar illness (CRDC-BP): rationale and validity
Authors: Ghaemi S. Nassir , Angst Jules , Vohringer Paul A. , Youngstrom Eric A. , Phelps James , Mitchell Philip B. , McIntyre Roger S. , Bauer Michael , Vieta Eduard , Gershon Samuel 
Published: October 2022

AbstractBackgroundIn the 1970 s, scientific research on psychiatric nosology was summarized in Research Diagnostic Criteria (RDC), based solely on empirical data, an important source for the third revision of the official nomenclature of the American Psychiatric Association in 1980, the Diagnostic and Statistical Manual, Third Edition (DSM-III). The intervening years, especially with the fourth edition in 1994, saw a shift to a more overtly “pragmatic” approach to diagnostic definitions, which were constructed for many purposes, with research evidence being only one consideration. The latest editions have been criticized as failing to be useful for research. Biological and clinical research rests on the validity of diagnostic definitions that are supported by firm empirical foundations, but critics note that DSM criteria have failed to prioritize research data in favor of “pragmatic” considerations.ResultsBased on prior work of the International Society for Bipolar Diagnostic Guidelines Task Force, we propose here Clinical Research Diagnostic Criteria for Bipolar Illness (CRDC–BP) for use in research studies, with the hope that these criteria may lead to further refinement of diagnostic definitions for other major mental illnesses in the future. New proposals are provided for mixed states, mood temperaments, and duration of episodes.ConclusionsA new CRDC could provide guidance toward an empirically-based, scientific psychiatric nosology, and provide an alternative clinical diagnostic approach to the DSM system.