bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liposomal delivery of gene therapy for ovarian cancer: a systematic review
Authors: Son Jin Sung , Chow Ryan , Kim Helena , Lieu Toney , Xiao Maria , Kim Sunny , Matuszewska Kathy , Pereira Madison , Nguyen David Le , Petrik Jim 
Published: August 2023

Abstract
Objective
To systematically identify and narratively synthesize the evidence surrounding liposomal delivery of gene therapy and the outcome for ovarian cancer.

Methods
An electronic database search of the Embase, MEDLINE and Web of Science from inception until July 7, 2023, was conducted to identify primary studies that investigated the effect of liposomal delivery of gene therapy on ovarian cancer outcomes. Retrieved studies were assessed against the eligibility criteria for inclusion.

Results
The search yielded 564 studies, of which 75 met the inclusion criteria. Four major types of liposomes were identified: cationic, neutral, polymer-coated, and ligand-targeted liposomes. The liposome with the most evidence involved cationic liposomes which are characterized by their positively charged phospholipids (n = 37, 49.3%). Similarly, those with neutrally charged phospholipids, such as 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine, were highly researched as well (n = 25, 33.3%). Eight areas of gene therapy research were identified, evaluating either target proteins/transcripts or molecular pathways: microRNAs, ephrin type-A receptor 2 (EphA2), interleukins, mitogen-activated protein kinase (MAPK), human-telomerase reverse transcriptase/E1A (hTERT/EA1), suicide gene, p53, and multidrug resistance mutation 1 (MDR1).

Conclusion
Liposomal delivery of gene therapy for ovarian cancer shows promise in many in vivo studies. Emerging polymer-coated and ligand-targeted liposomes have been gaining interest as they have been shown to have more stability and specificity. We found that gene therapy involving microRNAs was the most frequently studied. Overall, liposomal genetic therapy has been shown to reduce tumor size and weight and improve survivability. More research involving the delivery and targets of gene therapy for ovarian cancer may be a promising avenue to improve patient outcomes.
Acetylglutamine facilitates motor recovery and alleviates neuropathic pain after brachial plexus root avulsion in rats
Authors: Wu Lin , Chen Shuangxi , He Bing , Zhou Guijuan , Xu Yan , Zhu Guanghua , Xie Juan , Deng Limin , Wen Xuanwei , Li Sijing , Xiao Zijian 
Published: August 2023

Abstract
Background
Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms.

Methods
Male adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting.

Results
NAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA.

Conclusion
NAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA.
Partial gene suppression improves identification of cancer vulnerabilities when CRISPR-Cas9 knockout is pan-lethal
Authors: Krill-Burger J. Michael , Dempster Joshua M. , Borah Ashir A. , Paolella Brenton R. , Root David E. , Golub Todd R. , Boehm Jesse S. , Hahn William C. , McFarland James M. , Vazquez Francisca , Tsherniak Aviad 
Published: August 2023

Abstract
Background
Hundreds of functional genomic screens have been performed across a diverse set of cancer contexts, as part of efforts such as the Cancer Dependency Map, to identify gene dependencies—genes whose loss of function reduces cell viability or fitness. Recently, large-scale screening efforts have shifted from RNAi to CRISPR-Cas9, due to superior efficacy and specificity. However, many effective oncology drugs only partially inhibit their protein targets, leading us to question whether partial suppression of genes using RNAi could reveal cancer vulnerabilities that are missed by complete knockout using CRISPR-Cas9. Here, we compare CRISPR-Cas9 and RNAi dependency profiles of genes across approximately 400 matched cancer cell lines.

Results
We find that CRISPR screens accurately identify more gene dependencies per cell line, but the majority of each cell line’s dependencies are part of a set of 1867 genes that are shared dependencies across the entire collection (pan-lethals). While RNAi knockdown of about 30% of these genes is also pan-lethal, approximately 50% have selective dependency patterns across cell lines, suggesting they could still be cancer vulnerabilities. The accuracy of the unique RNAi selectivity is supported by associations to multi-omics profiles, drug sensitivity, and other expected co-dependencies.

Conclusions
Incorporating RNAi data for genes that are pan-lethal knockouts facilitates the discovery of a wider range of gene targets than could be detected using the CRISPR dataset alone. This can aid in the interpretation of contrasting results obtained from CRISPR and RNAi screens and reinforce the importance of partial gene suppression methods in building a cancer dependency map.
Long-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions
Authors: Tschernoster Nikolai , Erger Florian , Kohl Stefan , Reusch Björn , Wenzel Andrea , Walsh Stephen , Thiele Holger , Becker Christian , Franitza Marek , Bartram Malte P. , Kömhoff Martin , Schumacher Lena , Kukat Christian , Borodina Tatiana , Quedenau Claudia , Nürnberg Peter , Rinschen Markus M , Driller Jan H. , Pedersen Bjørn P. , Schlingmann Karl P. , Hüttel Bruno , Bockenhauer Detlef , Beck Bodo , Altmüller Janine 
Published: August 2023

Abstract
Background
Long-read sequencing is increasingly used to uncover structural variants in the human genome, both functionally neutral and deleterious. Structural variants occur more frequently in regions with a high homology or repetitive segments, and one rearrangement may predispose to additional events. Bartter syndrome type 3 (BS 3) is a monogenic tubulopathy caused by deleterious variants in the chloride channel gene CLCNKB, a high proportion of these being large gene deletions. Multiplex ligation-dependent probe amplification, the current diagnostic gold standard for this type of mutation, will indicate a simple homozygous gene deletion in biallelic deletion carriers. However, since the phenotypic spectrum of BS 3 is broad even among biallelic deletion carriers, we undertook a more detailed analysis of precise breakpoint regions and genomic structure.

Methods
Structural variants in 32 BS 3 patients from 29 families and one BS4b patient with CLCNKB deletions were investigated using long-read and synthetic long-read sequencing, as well as targeted long-read sequencing approaches.

Results
We report a ~3 kb duplication of 3′-UTR CLCNKB material transposed to the corresponding locus of the neighbouring CLCNKA gene, also found on ~50 % of alleles in healthy control individuals. This previously unknown common haplotype is significantly enriched in our cohort of patients with CLCNKB deletions (45 of 51 alleles with haplotype information, 2.2 kb and 3.0 kb transposition taken together, p=9.16×10−9). Breakpoint coordinates for the CLCNKB deletion were identifiable in 28 patients, with three being compound heterozygous. In total, eight different alleles were found, one of them a complex rearrangement with three breakpoint regions. Two patients had different CLCNKA/CLCNKB hybrid genes encoding a predicted CLCNKA/CLCNKB hybrid protein with likely residual function.

Conclusions
The presence of multiple different deletion alleles in our cohort suggests that large CLCNKB gene deletions originated from many independently recurring genomic events clustered in a few hot spots. The uncovered associated sequence transposition haplotype apparently predisposes to these additional events.
The spectrum of CLCNKB deletion alleles is broader than expected and likely still incomplete, but represents an obvious candidate for future genotype/phenotype association studies.
We suggest a sensitive and cost-efficient approach, consisting of indirect sequence capture and long-read sequencing, to analyse disease-relevant structural variant hotspots in general.
Cellular characterisation of advanced osteoarthritis knee synovium
Authors: Mimpen Jolet Y. , Hedley Robert , Ridley Anna , Baldwin Mathew J. , Windell Dylan , Bhalla Ananya , Ramos-Mucci Lorenzo , Buckley Christopher D. , Coles Mark C. , Alvand Abtin , Price Andrew J. , Carr Andrew J. , Dakin Stephanie G. , Snelling Sarah J. B. 
Published: August 2023

Abstract
Objectives
Osteoarthritis (OA) is increasingly recognised as a whole joint disease, with an important role for synovium. However, the repertoire of immune cells and fibroblasts that constitute OA synovium remains understudied. This study aims to characterise the cellular composition of advanced OA synovium and to explore potential correlations between different cell types and patient demographics or clinical scores.

Methods
Synovium, collected from 10 patients with advanced OA during total knee replacement surgery, was collagenase-digested, and cells were stained for flow cytometry analysis. Formalin-fixed paraffin-embedded synovium was sectioned, stained with immunofluorescence, and imaged using the multiplex Cell DIVE platform. Patient demographics and clinical scores were also collected.

Results
The proportion of immune cells in OA synovium varied between patients (8–38% of all cells). Macrophages and T cells were the dominant immune cell populations, together representing 76% of immune cells. Age positively correlated with the proportion of macrophages, and negatively correlated with T cells. CCR6+ T cells were found in 6/10 patients; these patients had a higher mean Kellgren-Lawrence grade across the three knee compartments. Immunofluorescence staining showed that macrophages were present in the lining as well as distributed throughout the sublining, while T and B cells were mainly localised near vessels in the sublining. Fibroblast subsets (CD45−PDPN+) based on the expression of CD34/CD90 or FAP/CD90 were identified in all patient samples, and some populations correlate with the percentage of immune cells or clinical scores. Immunofluorescence staining showed that FAP expression was particularly strong in the lining layer, but also present throughout the sublining layer. CD90 expression was exclusively found around vessels in the sublining, while CD34 was mostly found in the sublining but also occasionally in the lining layer.

Conclusions
There are significant differences in the relative proportions and subsets of immune cells in OA synovium; exploratory correlative analyses suggest that these differences might be correlated with age, clinical scores, or fibroblast subsets. Additional studies are required to understand how different cell types affect OA pathobiology, and if the presence or proportion of cell subsets relates to disease phenotypes.
Isolation and characterization of multidrug resistant Gallibacterium anatis biovar haemolytica strains from Polish geese and hens
Authors: Karwańska Magdalena , Wieliczko Alina , Bojesen Anders Miki , Villumsen Kasper Rømer , Krzyżewska-Dudek Eva , Woźniak-Biel Anna 
Published: August 2023

AbstractGallibacterium anatis biovar haemolytica is a bacterium that is frequently associated with infections of the reproductive tract and respiratory system in poultry. To assess the current prevalence and resistance profile of these bacteria in Poland, we collected and investigated 63 strains of Gallibacterium from diseased domestic poultry flocks including geese, laying hens, breeding hens and an ornamental hen. Detailed characterization of the isolates included the analysis of phenotypic antimicrobial resistance profiles and biofilm formation ability. Furthermore, the genetic background of 40 selected isolates regarding the presence of virulence and antimicrobial resistance genes and mobile genetic elements was determined. All investigated isolates were multidrug resistant, most prominently to β-lactams, fluoroquinolones, sulfonamides and macrolides. A total of 48 different resistance profiles were detected. Of all isolates, 50.8% formed a strong biofilm, where strains isolated from geese appeared to be better at biofilm formation than strains isolated from laying and breeding hens. Single-nucleotide polymorphism genotyping revealed that G. anatis bv. haemolytica strains are restricted in host and geographical distribution, and the geese isolates showed greater phylogenetic similarity. Whole genome sequencing enabled identification of 25 different antimicrobial resistance determinants. The most common resistance genes were tetB, blaROB-1, and blaTEM-1 which may be located on mobile genetic elements. All isolates possessed the toxin gene gtxA, and the fimbrial gene flfA was identified in 95% of strains. Our results indicated that all G. anatis bv. haemolytica isolates showed multidrug resistant phenotypes. Strains isolated from geese were characterized by the highest percentage of isolates resistant to selected antimicrobials, probably reflecting host-related adaptations.
ClpP protease modulates bacterial growth, stress response, and bacterial virulence in Brucella abortus
Authors: Sun Dongjie , Liu Yufu , Peng Xiaowei , Dong Hao , Jiang Hui , Fan Xuezheng , Feng Yu , Sun Jiali , Han Kun , Gao Qiang , Niu Jianrui , Ding Jiabo 
Published: August 2023

AbstractThe process of intracellular proteolysis through ATP-dependent proteases is a biologically conserved phenomenon. The stress responses and bacterial virulence of various pathogenic bacteria are associated with the ATP-dependent Clp protease. In this study, a Brucella abortus 2308 strain, ΔclpP, was constructed to characterize the function of ClpP peptidase. The growth of the ΔclpP mutant strain was significantly impaired in the TSB medium. The results showed that the ΔclpP mutant was sensitive to acidic pH stress, oxidative stress, high temperature, detergents, high osmotic environment, and iron deficient environment. Additionally, the deletion of clpP significantly affected Brucella virulence in macrophage and mouse infection models. Integrated transcriptomic and proteomic analyses of the ΔclpP strain showed that 1965 genes were significantly affected at the mRNA and/or protein levels. The RNA-seq analysis indicated that the ΔclpP strain exhibited distinct gene expression patterns related to energy production and conversion, cell wall/membrane/envelope biogenesis, carbohydrate transport, and metabolism. The iTRAQ analysis revealed that the differentially expressed proteins primarily participated in amino acid transport and metabolism, energy production and conversion, and secondary metabolites biosynthesis, transport and catabolism. This study provided insights into the preliminary molecular mechanism between Clp protease to bacterial growth, stress response, and bacterial virulence in Brucella strains.
Multimodal environmental cleaning strategies to prevent healthcare-associated infections
Authors: Browne Katrina , Mitchell Brett G 
Published: August 2023

AbstractInfection transmission in healthcare is multifaceted and by in large involves the complex interplay between a pathogen, a host and their environment. To prevent transmission, infection prevention strategies must also consider these complexities and incorporate targeted interventions aimed at all possible transmission pathways. One strategy to prevent and control infection is environmental cleaning. There are many aspects to an environmental cleaning strategy. We believe the key to successfully reducing the risk of healthcare-associated infections through the environment, is to design and implement a multimodal intervention. This paper aims to provide an overview of important considerations for designing a meaningful and sustainable environmental program for healthcare facilities.
Mechanism-based biomarkers for the quality control of Dangkwisoo-san: a scoping review
Authors: Lee Ji Hwan , Jin Shihui , Lee Myong Jin , Tran Nguyen Khoi Song , Kim Young-Joo , Lee Sanghyun , Kim Song-Yi , Kang Ki Sung 
Published: August 2023

AbstractDangkwisoo-san (DS) is a traditional Korean herbal medicine used to treat traumatic diseases, including pulmonary contusions, traumatic pneumothorax, bruising, and ankle sprain. Quality control (QC) biomarkers for DS can help ensure its safety and efficacy. Although chemical quality assessments are performed to ensure consistent efficacy of DS, the identity and quantity of the compounds contained within a given natural product is a frequent complication. We conducted a literature review to identify biological assays that support the chemical QC of DS. The results of our investigation confirmed that in vitro experiments with aqueous and alcoholic extracts of DS exhibited positive effects on many aspects of treatment. With 80% EtOH extraction, a low concentration of DS (1 μg/ml) significantly diminished the expression of inflammatory factors, such as nitric oxide (NO), TNF-α, IL-1β, and IL-6, in the Raw264.7 cell line. MeOH extracts activated NRF2 and antioxidant activities in response to the inflammatory inducer LPS, and water extracts of DS remarkably reduced proinflammatory cytokine levels compared to dexamethasone and cyclosporin treatments. Aqueous extracts of DS at a moderate dose of 125 μg/ml supported bone regeneration, recovered ischemic injury in an eNOS-dependent manner, and prevented metabolic disorders (TRPM7 channel inhibition). Cytokines, NO, and immunoglobulins are potential biological QC biomarkers to assess the anti-inflammation and immune response to DS. Future quality evaluation studies of herbal medicines (herbal prescriptions) should aim to select the mechanism-based in vitro efficacy evaluation methods that can estimate consistent clinical effects.
Recent trends in agri-food Made in Italy exports
Authors: Carbone Anna , Henke Roberto 
Published: August 2023

AbstractThe agri-food sector is a key component of the Italian economy and the Made in Italy products are altogether the core of it with a strong export propensity. This paper analyses the recent export performance of the Made in Italy as a whole and at product level. The analysis is based on the conjoint measure of export specialization (RCA) and sophistication (Prody). Results show that the Made in Italy aggregate is performing well but, at the same time, which single products face significant difficulties. On the one hand, this is the case for those items for which Italy is improving its specialization, but international competition is increasingly based on price, thus reducing profitability (e. g. prepared vegetables, chocolate products, blue cheeses). On the other hand, there are products whose sophistication is growing, and remuneration perspectives rise with it, but for which Italy is eroding its comparative advantage (e. g. ice creams, pasta, grape and wine > 2lt).
Long-read assembled metagenomic approaches improve our understanding on metabolic potentials of microbial community in mangrove sediments
Authors: Zhang Zhi-Feng , Liu Li-Rui , Pan Yue-Ping , Pan Jie , Li Meng 
Published: August 2023

Abstract
Background
Mangrove wetlands are coastal ecosystems with important ecological features and provide habitats for diverse microorganisms with key roles in nutrient and biogeochemical cycling. However, the overall metabolic potentials and ecological roles of microbial community in mangrove sediment are remained unanswered. In current study, the microbial and metabolic profiles of prokaryotic and fungal communities in mangrove sediments were investigated using metagenomic analysis based on PacBio single-molecule real time (SMRT) and Illumina sequencing techniques.

Results
Comparing to Illumina short reads, the incorporation of PacBio long reads significantly contributed to more contiguous assemblies, yielded more than doubled high-quality metagenome-assembled genomes (MAGs), and improved the novelty of the MAGs. Further metabolic reconstruction for recovered MAGs showed that prokaryotes potentially played an essential role in carbon cycling in mangrove sediment, displaying versatile metabolic potential for degrading organic carbons, fermentation, autotrophy, and carbon fixation. Mangrove fungi also functioned as a player in carbon cycling, potentially involved in the degradation of various carbohydrate and peptide substrates. Notably, a new candidate bacterial phylum named as Candidatus Cosmopoliota with a ubiquitous distribution is proposed. Genomic analysis revealed that this new phylum is capable of utilizing various types of organic substrates, anaerobic fermentation, and carbon fixation with the Wood-Ljungdahl (WL) pathway and the reverse tricarboxylic acid (rTCA) cycle.

Conclusions
The study not only highlights the advantages of HiSeq-PacBio Hybrid assembly for a more complete profiling of environmental microbiomes but also expands our understanding of the microbial diversity and potential roles of distinct microbial groups in biogeochemical cycling in mangrove sediment.
Extracting chain lines and laid lines from digital images of medieval paper using spectral total variation decomposition
Authors: Grossmann Tamara G. , Schönlieb Carola-Bibiane , Da Rold Orietta 
Published: August 2023

Abstract
Medieval paper, a handmade product, is made with a mould which leaves an indelible imprint on the sheet of paper. This imprint includes chain lines, laid lines and watermarks which are often visible on the sheet. Extracting these features allows the identification of the paper stock and gives information about the chronology, localisation and movement of manuscripts and people. Most computational work for feature extraction of paper analysis has so far focused on radiography or transmitted light images. While these imaging methods provide clear visualisation of the features of interest, they are expensive and time consuming in their acquisition and not feasible for smaller institutions. However, reflected light images of medieval paper manuscripts are abundant and possibly cheaper in their acquisition. In this paper, we propose algorithms to detect and extract the laid and chain lines from reflected light images. We tackle the main drawback of reflected light images, that is, the low contrast attenuation of chain and laid lines and intensity jumps due to noise and degradation, by employing the spectral total variation decomposition and develop methods for subsequent chain and laid line extraction. Our results clearly demonstrate the feasibility of using reflected light images in paper analysis. This work enables feature extraction for paper manuscripts that have otherwise not been analysed due to a lack of appropriate images. We also open the door for paper stock identification at scale.