bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Cytologic Sample Preparations for Compatibility With Nucleic Acid Analysis
Authors: Sorber Laure , Claes Bart , Zwaenepoel Karen , Van Dorst Bieke , De Winne Koen , Fransen Els , Wener Reinier , Lapperre Therese , Lardon Filip , Pauwels Patrick
Published: June 2021

Objectives

In this study, the influence of several key elements of the cytologic sample workflow on DNA and RNA content was evaluated.

Methods

The A549 cell line, patient-derived organoids, and pleural effusions were used to investigate the effect of (1) several collection media and delayed time to processing; (2) cytology specimens; (3) cytologic staining; and (4) formalin-fixed, paraffin-embedded (FFPE) cell block processing on nucleic acid quality and quantity as determined by fragment analyzer, Qubit analysis (Thermo Fisher Scientific), and quantitative polymerase chain reaction–based analysis on the Idylla platform (Biocartis).

Results

Alcohol-based collection media (CytoRich Red [Thermo Fisher Scientific] and EtOH95%) displayed high DNA and RNA preservation capacity, while phosphate-buffered saline and, to a lesser extent, formalin were associated with high RNA quality. Cytospin and smear cytology specimens were subject to DNA and RNA loss. Cytologic staining had no further impact on sample quality, hence destaining is not necessary. Both H&E-stained and unstained FFPE sections are compatible with nucleic acid analysis, despite a strong decrease in DNA and RNA quality.

Conclusions

Although several key elements of the cytologic sample workflow have an influence on DNA and RNA quality and quantity, the selection of these elements is also dependent on the downstream (ancillary) testing methods.
QuantifyPoly(A): reshaping alternative polyadenylation landscapes of eukaryotes with weighted density peak clustering
Authors: Ye Congting , Zhao Danhui , Ye Wenbin , Wu Xiaohui , Ji Guoli , Li Qingshun Q , Lin Juncheng
Published: June 2021

The dynamic choice of different polyadenylation sites in a gene is referred to as alternative polyadenylation, which functions in many important biological processes. Large-scale messenger RNA 3′ end sequencing has revealed that cleavage sites for polyadenylation are presented with microheterogeneity. To date, the conventional determination of polyadenylation site clusters is subjective and arbitrary, leading to inaccurate annotations. Here, we present a weighted density peak clustering method, QuantifyPoly(A), to accurately quantify genome-wide polyadenylation choices. Applying QuantifyPoly(A) on published 3′ end sequencing datasets from both animals and plants, their polyadenylation profiles are reshaped into myriads of novel polyadenylation site clusters. Most of these novel polyadenylation site clusters show significantly dynamic usage across different biological samples or associate with binding sites of trans-acting factors. Upstream sequences of these clusters are enriched with polyadenylation signals UGUA, UAAA and/or AAUAAA in a species-dependent manner. Polyadenylation site clusters also exhibit species specificity, while plants ones generally show higher microheterogeneity than that of animals. QuantifyPoly(A) is broadly applicable to any types of 3′ end sequencing data and species for accurate quantification and construction of the complex and dynamic polyadenylation landscape and enables us to decode alternative polyadenylation events invisible to conventional methods at a much higher resolution.
Deep learning-based real-time detection of novel pathogens during sequencing
Authors: Bartoszewicz Jakub M , Genske Ulrich , Renard Bernhard Y
Published: June 2021

Novel pathogens evolve quickly and may emerge rapidly, causing dangerous outbreaks or even global pandemics. Next-generation sequencing is the state of the art in open-view pathogen detection, and one of the few methods available at the earliest stages of an epidemic, even when the biological threat is unknown. Analyzing the samples as the sequencer is running can greatly reduce the turnaround time, but existing tools rely on close matches to lists of known pathogens and perform poorly on novel species. Machine learning approaches can predict if single reads originate from more distant, unknown pathogens but require relatively long input sequences and processed data from a finished sequencing run. Incomplete sequences contain less information, leading to a trade-off between sequencing time and detection accuracy. Using a workflow for real-time pathogenic potential prediction, we investigate which subsequences already allow accurate inference. We train deep neural networks to classify Illumina and Nanopore reads and integrate the models with HiLive2, a real-time Illumina mapper. This approach outperforms alternatives based on machine learning and sequence alignment on simulated and real data, including SARS-CoV-2 sequencing runs. After just 50 Illumina cycles, we observe an 80-fold sensitivity increase compared to real-time mapping. The first 250 bp of Nanopore reads, corresponding to 0.5 s of sequencing time, are enough to yield predictions more accurate than mapping the finished long reads. The approach could also be used for screening synthetic sequences against biosecurity threats.
Elucidation of dynamic microRNA regulations in cancer progression using integrative machine learning
Authors: Dogan Haluk , Hakguder Zeynep , Madadjim Roland , Scott Stephen , Pierobon Massimiliano , Cui Juan
Published: June 2021

Motivation

Empowered by advanced genomics discovery tools, recent biomedical research has produced a massive amount of genomic data on (post-)transcriptional regulations related to transcription factors, microRNAs, long non-coding RNAs, epigenetic modifications and genetic variations. Computational modeling, as an essential research method, has generated promising testable quantitative models that represent complex interplay among different gene regulatory mechanisms based on these data in many biological systems. However, given the dynamic changes of interactome in chaotic systems such as cancers, and the dramatic growth of heterogeneous data on this topic, such promise has encountered unprecedented challenges in terms of model complexity and scalability. In this study, we introduce a new integrative machine learning approach that can infer multifaceted gene regulations in cancers with a particular focus on microRNA regulation. In addition to new strategies for data integration and graphical model fusion, a supervised deep learning model was integrated to identify conditional microRNA-mRNA interactions across different cancer stages.

Results

In a case study of human breast cancer, we have identified distinct gene regulatory networks associated with four progressive stages. The subsequent functional analysis focusing on microRNA-mediated dysregulation across stages has revealed significant changes in major cancer hallmarks, as well as novel pathological signaling and metabolic processes, which shed light on microRNAs’ regulatory roles in breast cancer progression. We believe this integrative model can be a robust and effective discovery tool to understand key regulatory characteristics in complex biological systems.

Availability

http://sbbi-panda.unl.edu/pin/
Extracellular vesicles derived from cancer-associated fibroblast carries miR-224-5p targeting SLC4A4 to promote the proliferation, invasion and migration of colorectal cancer cells
Authors: Zheng Yu , Zeng Jintao , Lin Dajia , Xia Haoyun , Wang Xiangyu , Chen Liqi , Chen Hongyuan , Huang Liangxiang , Zeng Changqing
Published: June 2021

More and more studies indicated that extracellular vesicles (EVs) carrying miRNAs have been potential biomarkers of various cancers including colorectal cancer (CRC). This study aims to explore the function of miR-224-5p carried by EVs derived from cancer-associated fibroblasts (CAFs) in CRC. Here, we found that miR-224-5p was highly expressed while SLC4A4 was lowly expressed in CRC cells. Moreover, dual-luciferase reporter gene assay testified that miR-224-5p targeted SLC4A4. The expression of miR-224-5p in CAFs-derived EVs was found to be elevated. It was also testified that CAFs-derived EVs could transfer miR-224-5p into CRC cells. miR-224-5p in CAFs-derived EVs facilitated the proliferation, migration, invasion and anti-apoptosis of CRC cells. Overexpressing miR-224-5p increased the proliferative, migratory and invasive abilities of CRC cells and inhibit CRC cell apoptosis, while overexpressing SLC4A4 caused the opposite result. Research in vitro and in vivo further indicated that miR-224-5p promoted CRC cell progression via binding to its downstream target gene SLC4A4. Rescue assay also demonstrated that overexpressing miR-224-5p reversed the inhibitory effect of overexpressed SLC4A4 on cancer cell growth. In addition, in vivo assay identified that high level of miR-224-5p promoted the growth of cancer cells in mice in vivo. In conclusion, we explored the effect of miR-224-5p in CRC, which helps for further exploration of new methods for CRC targeted therapy.
“K-pop is Rupturing Chilean Society”: Fighting With Globalized Objects in Localized Conflicts
Authors: Diaz Pino Camilo
Published: June 2021

Amid a rapidly growing wave of anti-neoliberal protest emerging in late 2019, Chile’s government scrambled to respond to the massive scale of this dissidence by attempting to find some external agent to pin the blame on. Initially seeking evidence of Venezuelan or Russian involvement, the state eventually pinned the blame on K-pop as an agent of “social rupture.” This article examines this framing of K-pop by Chilean authorities and what this says about the position of Korean media’s integration into a Latin American pop-culture landscape that is growing ever more globalized and non-Western. It likewise examines the contestatory embracing of K-pop by Chilean anti-neoliberal activists, their broader integration of globalized cultural objects, and how this reflects on wider current anti-neoliberal activist cultures operating in the Global South.
Cortical Morphology in Autism: Findings from a Cortical Shape-Adaptive Approach to Local Gyrification Indexing
Authors: Zoltowski Alisa R , Lyu Ilwoo , Failla Michelle , Mash Lisa E , Dunham Kacie , Feldman Jacob I , Woynaroski Tiffany G , Wallace Mark T , Barquero Laura A , Nguyen Tin Q , Cutting Laurie E , Kang Hakmook , Landman Bennett A , Cascio Carissa J
Published: June 2021

It has been challenging to elucidate the differences in brain structure that underlie behavioral features of autism. Prior studies have begun to identify patterns of changes in autism across multiple structural indices, including cortical thickness, local gyrification, and sulcal depth. However, common approaches to local gyrification indexing used in prior studies have been limited by low spatial resolution relative to functional brain topography. In this study, we analyze the aforementioned structural indices, utilizing a new method of local gyrification indexing that quantifies this index adaptively in relation to specific sulci/gyri, improving interpretation with respect to functional organization. Our sample included n = 115 autistic and n = 254 neurotypical participants aged 5–54, and we investigated structural patterns by group, age, and autism-related behaviors. Differing structural patterns by group emerged in many regions, with age moderating group differences particularly in frontal and limbic regions. There were also several regions, particularly in sensory areas, in which one or more of the structural indices of interest either positively or negatively covaried with autism-related behaviors. Given the advantages of this approach, future studies may benefit from its application in hypothesis-driven examinations of specific brain regions and/or longitudinal studies to assess brain development in autism.
Using Patient Completed Screening Tools to Predict Risk of Malnutrition in Patients With Inflammatory Bowel Disease
Authors: Taylor Lorian M , Eslamparast Tannaz , Farhat Kamal , Kroeker Karen , Halloran Brendan , Shommu Nusrat , Kumar Ankush , Fitzgerald Quinn , Gramlich Leah , Abraldes Juan G , Tandon Puneeta , Raman Maitreyi
Published: June 2021

Background

Malnutrition is associated with adverse clinical outcomes in patients with inflammatory bowel disease (IBD), however, malnutrition screening is not routinely performed. This study aimed to identify the prevalence of malnutrition in patients with IBD and compare the accuracy of patient completed screens to a gold-standard malnutrition assessment tool: the dietitian-completed subjective global assessment (SGA).

Methods

This cross-sectional study was conducted at 2 hospitals and 2 ambulatory care clinics in Alberta, Canada. Patients with IBD completed 4 malnutrition screening tools: abridged patient-generated SGA (abPG-SGA), Malnutrition Universal Screening Tool (MUST), Canadian Nutrition Screening Tool (CNST), and Saskatchewan IBD–nutrition risk (SaskIBD-NR). Risk of malnutrition was calculated for each tool and differences were compared between IBD subtype and body mass index (BMI) categories. Sensitivity and specificity, negative and positive predictive values (NPV and PPV), and area under the receiver operating characteristic curve (AUC) were calculated compared to SGA.

Results

Patients with Crohn’s disease (n = 149) and ulcerative colitis (n = 96) participated in this study. Overall prevalence of malnutrition using SGA was 23% and malnutrition risk for CNST, abPG-SGA, SaskIBD-NR, and MUST was 37%, 36%, 36%, and 27%, respectively. Overall, the abPG-SGA had the highest sensitivity (83%), PPV (53%), and NPV (94%), and largest AUC (0.837) compared to SGA. For patients with a BMI ≥25 kg/m2, sensitivity and PPV of the abPG-SGA decreased to 73% and 41%, respectively, with a AUC of 0.841.

Conclusions

Malnutrition is prevalent in patients with IBD and using malnutrition risk screening tools such as the abPG-SGA may be useful to identify patients who would benefit from further assessment.
Treatment and posttreatment effects of Herbst appliance therapy on trabecular structure of the mandible using fractal dimension analysis
Authors: Amuk Mehmet , Gul Amuk Nisa , Yılmaz Serkan
Published: June 2021

Objectives

This controlled study aimed to evaluate the effects of Herbst therapy on the trabecular structure of the condyle and angulus mandible using fractal dimension analysis (FD-A) accompanied by skeletal cephalometric changes.

Material and method

The panoramic and cephalometric radiographs of 30 patients with skeletal Class II malocclusion treated with the Herbst appliance (C II-H group, mean age: 15.23 ± 1.08), 30 patients with skeletal Class II malocclusion that received fixed orthodontic treatment (C II-C group, mean age: 15.73 ± 1.38), and 30 patients with skeletal Class I malocclusion (C I-C group, mean age: 15.90 ± 1.30) were selected. FD-A was performed on the superoposterior region (C-SP) and centre of the condyles (C-C) and the mandibular angulus (Ang) on the panoramic radiographs taken at the pretreatment (T0), intermediate stage of treatment (T1), and posttreatment (T2) timepoints just like cephalometric analysis.

Results

Herbst therapy provided a statistically significant increase in SNB, ANS-Me, Na-Me, S-Go, Co-Gn and a decrease in ANB and overjet (P < 0.05). All skeletal changes remained stable during the fixed appliance treatment after Herbst. The FD values in C-C increased (P < 0.05), and C-SP values decreased (P < 0.05) during Herbst therapy, while after removal of the Herbst appliance, no significant change was observed despite an increase in C-SP. The Ang value did not change during Herbst treatment, but then increased significantly (P < 0.05). There was no significant change in the FD values of the C I-C and C II-C groups at any stage of treatment. The C-C and C-SP changes at T1–T0 period, C-SP and Ang changes at T2–T1 period, and C-C, C-SP, and Ang values at T2–T0 period were found higher in C II-H group compared with the C II-C group significantly (P < 0.05).

Conclusion

Herbst therapy changed the trabecular structure of the condyles in different directions at the superoposterior and central regions of the condyles, while the structural complexity of the angulus mandible, which did not change during the Herbst treatment, increased during the fixed orthodontic treatment after Herbst.
Lack of specialist care is associated with increased morbidity and mortality in adult congenital heart disease: a population-based study
Authors: Diller Gerhard-Paul , Orwat Stefan , Lammers Astrid Elisabeth , Radke Robert M , De-Torres-Alba Fernando , Schmidt Renate , Marschall Ursula , Bauer Ulrike M , Enders Dominic , Bronstein Leo , Kaleschke Gerrit , Baumgartner Helmut
Published: June 2021

Aims

The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population.

Methods and results

Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients (<70 years of age) were included. Patients were stratified into those followed exclusively by primary care physicians (PCPs) and those with additional cardiology follow-up between 2014 and 2016. Associations between level of care and outcome were assessed by multivariable/propensity score Cox analyses. Overall, 24 139 patients (median age 43 years, 54.8% female) were included. Of these, only 49.7% had cardiology follow-up during the 3-year period, with 49.2% of patients only being cared for by PCPs and 1.1% having no contact with either. After comprehensive multivariable and propensity score adjustment, ACHD patients under cardiology follow-up had a significantly lower risk of death [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.67–0.98; P = 0.03) or major events (HR 0.85, 95% CI 0.78–0.92; P < 0.001) compared to those only followed by PCPs. At 3-year follow-up, the absolute risk difference for mortality was 0.9% higher in ACHD patients with moderate/severe complexity lesions cared by PCPs compared to those under cardiology follow-up.

Conclusion

Cardiology care compared with primary care is associated with superior survival and lower rates of major complications in ACHD. It is alarming that even in a high resource setting with well-established specialist ACHD care approximately 50% of contemporary ACHD patients are still not linked to regular cardiac care. Almost all patients had at least one contact with a PCP during the study period, suggesting that opportunities to refer patients to cardiac specialists were missed at PCP level. More efforts are required to alert PCPs and patients to appropriate ACHD care.
Jan Huygen van Linschoten and the Reys-gheschrift: updating Iberian Science for the Dutch expansion
Authors: Vila-Santa Nuno
Published: June 2021

In 1596 Jan Huygen van Linschoten published his Itinerario. It contained a section called the Reys-gheschrift, which was the first nautical compendium to include sailing routes on the earth’s three main oceans. This publication enabled the Dutch and the English to launch successful maritime strategies. In this article I discuss how Iberian Science, mainly its sources, was employed in the Reys-gheschrift, as well as the major changes made prior to publication and the reasons why Linschoten introduced them. These topics are connected with a major debate concerning the drive for geographical knowledge, in which I attempt to demonstrate the importance of Iberian Science for the onset of the Dutch maritime expansion and for European seamanship more broadly in the sixteenth and seventeenth centuries.
GWAS in Africans identifies novel lipids loci and demonstrates heterogenous association within Africa
Authors: Bentley Amy R , Chen Guanjie , Doumatey Ayo P , Shriner Daniel , Meeks Karlijn A C , Gouveia Mateus H , Ekoru Kenneth , Zhou Jie , Adeyemo Adebowale , Rotimi Charles N
Published: June 2021

Serum lipids are biomarkers of cardiometabolic disease risk, and understanding genomic factors contributing to their distribution is of interest. Studies of lipids in Africans are rare, though it is expected that such studies could identify novel loci. We conducted a GWAS of 4317 Africans enrolled from Nigeria, Ghana and Kenya. We evaluated linear mixed models of high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), total cholesterol (CHOL), triglycerides (TG) and TG/HDLC. Replication was attempted in 9542 African Americans (AA).

In our main analysis, we identified 28 novel associations in Africans. Of the 18 of these that could be tested in AA, three associations replicated (GPNMB-TG, ENPP1-TG and SMARCA4-LDLC). Five additional novel loci were discovered upon meta-analysis with AA (rs138282551-TG, PGBD5-HDLC, CD80-TG/HDLC, SLC44A1-CHOL and TLL2-CHOL). Analyses considering only those with predominantly West African ancestry (Nigeria, Ghana and AA) yielded new insights: ORC5-LDLC and chr20:60973327-CHOL.

Among our novel findings are some loci with known connections to lipids pathways. For instance, rs147706369 (TLL2) alters a regulatory motif for sterol regulatory element-binding proteins, a family of transcription factors that control the expression of a range of enzymes involved in cholesterol, fatty acid and TG synthesis, and rs115749422 (SMARCA4), an independent association near the known LDLR locus that is rare or absent in populations without African ancestry. These findings demonstrate the utility of conducting genomic analyses in Africans for discovering novel loci and provide some preliminary evidence for caution against treating ‘African ancestry’ as a monolithic category.
Neural guidance factors as hubs of immunometabolic cross-talk
Authors: Nakanishi Yoshimitsu , Kang Sujin , Kumanogoh Atsushi
Published: June 2021

Semaphorins were originally identified as axon-guidance molecules essential for neural development. In addition to their functions in the neural system, members of the semaphorin family have critical functions in many pathophysiological processes, including immune responses, bone homeostasis, cancer and metabolic disorders. In particular, several lines of evidence indicate that mammalian/mechanistic target of rapamycin (mTOR), a central regulator of cell metabolism, regulates the functions of semaphorins in various types of cells, revealing a novel link between semaphorins and cell metabolism. In this review, we discuss recent advances in the immunometabolic functions of semaphorins, with a particular focus on mTOR signaling.
Differences in Mate Pairings of Hatchery- and Natural-Origin Coho Salmon Inferred from Offspring Genotypes
Authors: Auld H L , Jacobson D P , Rhodes A C , Banks M A
Published: June 2021

Synopsis

Captive breeding can affect how sexual selection acts on subsequent generations. One context where this is important is in fish hatcheries. In many salmon hatcheries, spawning is controlled artificially and offspring are reared in captivity before release into the wild. While previous studies have suggested that hatchery- and natural-origin fish may make different mate choice decisions, it remains to be determined how hatchery fish may be making different mate choice decisions compared with natural-origin fish at a genetic level. Using genotyping-by-sequencing, we identify single-nucleotide polymorphisms (SNPs) associated with variation in mate pairings from a natural context involving hatchery- and natural-origin coho salmon (Oncorhynchus kisutch). In both natural-origin and hatchery mate pairs, we observed more SNPs with negative assortment than positive assortment. However, only 3% of the negative assortment SNPs were shared between the two mating groups, and 1% of the positive assortment SNPs were shared between the two mating groups, indicating divergence in mating cues between wild and hatchery-raised salmon. These findings shed light on mate choice in general and may have important implications in the conservation management of species as well as for improving other captive breeding scenarios. There remains much to discover about mate choice in salmon and research described here reflects our intent to test the potential of ongoing advances in population genomics to develop new hatchery practices that may improve the performance of hatchery offspring, lessening the differences and thus potential impacts upon wild stocks.
Can UN Peacekeeping Promote Environmental Quality?
Authors: Bakaki Zorzeta , Böhmelt Tobias
Published: June 2021

This research focuses on a positive, and previously largely unknown, implication of United Nations (UN) peacekeeping: better environmental quality. While maintaining international peace and security remains the main goal of peacekeeping operations, we contend that they can also be linked to environmentally friendly outcomes. Mission mandates and UN policies increasingly comprise actions that potentially promote environmental quality. At the same time, positive side effects on the environment materialize due to the cooperation with and activities of other UN bodies. The empirical analyses, also correcting for the likely non-random assignment of peace missions and employing several alternative outcome measures, suggest that UN peace missions are indeed substantively associated with better environmental quality. This research has important implications for our understanding of peacekeeping operations, and it contributes to the literatures on the (unintended) consequences of peacekeeping as well as environmental politics.
Practice Approaches to the Digital Transformations of Diplomacy: Toward a New Research Agenda
Authors: Hedling Elsa , Bremberg Niklas
Published: June 2021

As a growing number of diplomatic practices take new digital forms, research on digital diplomacy is rapidly expanding. Many of the changes linked to digitalization transform or challenge traditional ways of doing diplomacy. Analyses of new forms of “digital diplomacy” are therefore valuable for the advancement of practice approaches in international relations theory. That said, digital diplomacy poses a number of challenges for international relations scholarship that are only beginning to be addressed. Digitalization is both a process and a result, and provokes key questions regarding continuity, change, agency, space, and materiality in diplomacy. The overarching aim of this article is to advance a research agenda that seeks to address key questions in the study of digital diplomacy on the basis of various practice approaches. In particular, the article highlights three dimensions of change as being central to the research agenda and investigates how these can be explored in future analyses of digital diplomacy.
Molecular Identification of Leafmining Flies From Australia Including New Liriomyza Outbreaks
Authors: Xu Xuefen , Coquilleau Marianne P , Ridland Peter M , Umina Paul A , Yang Qiong , Hoffmann Ary A
Published: June 2021

Some leafmining fly species are pests of agricultural and ornamental plants but they also include many species with little economic importance. The taxonomy of leafmining flies is often challenging because of putative cryptic species. Following new outbreaks of Liriomyza (Diptera:Agromyzidae) in Australia, we here characterize 13 dipteran leafminer species collected from Australia based on cytochrome c oxidase subunit 1 (COI) DNA barcodes, and we compare these with overseas data. We confirm barcodes of nine species from the Agromyzidae (Liriomyza sativae, L. huidobrensis, L. trifolii, L. bryoniae, L. chinensis, L. brassicae, L. chenopodii, Phytomyza plantaginis and P. syngenesiae) and one species from the Drosophilidae (Scaptomyza flava); we describe new haplotypes for some of these species. Furthermore, we provide the first DNA barcodes for two species (Cerodontha milleri and Phytoliriomyza praecellens) from the Agromyzidae and one species (Scaptomyza australis) from the Drosophilidae. These findings provide a baseline for DNA-based identification of pest Liriomyza incursions spreading across the Australian east coast in relation to other species already present in Australia.
Financial Incentives and Competitive Pressure: The Case of the Hospital Industry
Authors: Choné Philippe , Wilner Lionel
Published: June 2021

In the late 2000s, a regulatory reform dramatically strengthened the incentives of French nonprofit (NP) hospitals to attract patients. Exploiting exhaustive data for surgery treatments between 2005 and 2008, and modeling hospitals as supplying utility to patients, we show that increased competitive pressure on NP hospitals caused them to perform more procedures, but did not inflate overall activity at the industry level. Although they have gained market shares over their for-profit (FP) counterparts, NP hospitals have been significantly worse off after the reform. To adjust to stronger financial incentives, they incurred an additional effort (pecuniary and non-pecuniary costs) equivalent to about a quarter of their annual revenue.
Emerging technologies for cervical cancer screening
Authors: Hamashima Chisato
Published: June 2021

Cervical cancer remains a concern worldwide, and cervical cancer screening plays an important role in reducing the burden of this disease. Although cytology is still the main strategy for cervical cancer screening, it has gradually changed to human papillomavirus testing. The specificity of human papillomavirus testing is lower than that of cytology, which leads to an increased rate of colposcopy after positive results. To decrease colposcopic examinations, an efficient triage method is needed for human papillomavirus screening. New biomarkers have been developed and evaluated for primary screening and triage of abnormal cytology or human papillomavirus-positive results. Their sensitivity and specificity were estimated and compared with those of cytology. In the present study, the following new techniques were examined: p16/Ki67 dual staining, DNA methylation, micro-ribonucleic acid, chromosomal abnormalities, Claudins and DNA ploidy. Evaluation studies of p16/Ki67 dual staining and DNA methylation were more advanced than those of other options. When p16/Ki67 dual staining was used for triage for human papillomavirus testing, the sensitivity of 2 or greater cervical intraepithelial neoplasia (CIN2+) detection was higher than that of cytology without decreased specificity. Although there are several types of DNA methylation, sensitivity and specificity were moderate for detecting CIN2+. S5 classifier is a commercialized product that consists of viral methylation, and high sensitivity with decreased specificity has been reported. Considering its combination with self-sampling, DNA methylation is a highly anticipated technique along with human papillomavirus testing for the next generation of cervical cancer screening. However, the backgrounds for cervical cancer screening differ among countries and further study is needed to identify the best available method.
In-silico HMG-CoA reductase-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin
Authors: Metibemu Damilohun Samuel , Akinloye Oluseyi Adeboye , Akamo Adio Jamiu , Okoye Jude Ogechukwu , Omotuyi Idowu Olaposi
Published: June 2021

Objectives

Inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate rate-determining enzyme for the biogenesis of cholesterol is known to show antineoplastic effects. Therefore, this study investigates the in-silico HMG-CoA reductase (HMGCR)-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin.

Methods

Carotenoids from S. mombin leaves were characterized with the aid of liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS). The characterized phytochemicals were obtained from PubChem. They were docked into the orthosteric site of human HMGCR (Protein Data Bank code 1HW8) using AutoDock 4.0 suites. DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer was treated with the carotenoids extract from S. mombin (100 mg/kg and 200 mg/kg doses) to assess its anti-lipidaemic cum anticancer effects.

Key findings

Carotenoids from S. mombin; beta-carotene-15,15′-epoxide, astaxanthin and 7,7′,8,8′-tetrahydro-β-β-carotene demonstrate HMGCR inhibition. They form hydrophobic interactions with key residues within the catalytic domain of HMGCR. The carotenoids extract exhibits anti-lipidaemic/anticancer effects, lowering serum triglyceride, LDL and cholesterol concentration. It increases HDL concentration and downregulates the expression of HMGR, AFP, CEACAM-3, BRCA-1 and HIF-1 mRNAs.

Conclusion

Carotenoids from S. mombin demonstrate HMG-CoA reductase (HMGCR) inhibition, anti-lipidaemic, and anticancer effects. The inhibition of HMGCR by the carotenoids extract further poses it as a potential anti-hypercholesterolaemia compounds.
Malignant phyllodes tumor with synchronous metastases to axillary lymph nodes, lung at the presentation: a case report and literature review
Authors: Le Quang Hong , Mai Vuong The
Published: June 2021

Phyllodes tumors are rare mesenchymal tumors of breast. Malignant phyllodes tumors can develop metastases to distal organs with spreading hematogenously to most frequent sites as lungs, bone and brain. Regional lymph node enlargement is common but metastasis to lymph node is a very rare phenomenon with prevalence about 1.1–3.8%. In this report, we introduce a case of malignant phyllodes tumor of breast in 57-year-old female patient. Synchronous metastases to axillary lymph nodes and lung were found at the presentation. She was treated with mastectomy combined with axillary lymph node dissection and adjuvant chemotherapy. Axillary lymph node dissection can be considered in case of proven metastatic or suspiciously palpable lymph nodes.
Renal hydatidosis masquerading as xanthogranulomatous pyelonephritis: a new case report
Authors: Hermi Amine , Ouanes Yassine , Tapsoba Abdoulkader , Zehani Alia Kassar , Chaker Kays , Bibi Mokhtar , Daly Kheireddine Mrad , Sellami Ahmed , Rhouma Sami Ben , Nouira Yassine
Published: June 2021

Human hydatid disease is still endemic in pastoral and rangeland areas, with temperate climate, mainly in the southern shore of the Mediterranean, particularly in the Maghreb countries. Renal localization is rare although it is the most frequent site of the urinary tract. Its clinical evolution remains silent for long time, and the diagnosis is often elusive for years. Renal hydatid cysts may pose a problem of differential diagnosis. Our case concerns a renal hydatidosis misdiagnosed as a xanthogranulomatous pyelonephritis, treated by total nephrectomy.
Multiwavelength continuum sizes of protoplanetary discs: scaling relations and implications for grain growth and radial drift
Authors: Tazzari M , Clarke C J , Testi L , Williams J P , Facchini S , Manara C F , Natta A , Rosotti G
Published: June 2021

We analyse spatially resolved ALMA observations at 0.9, 1.3, and 3.1 mm for the 26 brightest protoplanetary discs in the Lupus star-forming region. We characterize the discs multiwavelength brightness profiles by fitting the interferometric visibilities in a homogeneous way, obtaining effective disc sizes at the three wavelengths, spectral index profiles, and optical depth estimates. We report three fundamental discoveries: first, the millimetre continuum size–luminosity relation already observed at 0.9 mm is also present at 1.3 mm with an identical slope, and at 3.1 mm with a steeper slope, confirming that emission at longer wavelengths becomes increasingly optically thin. Second, when observed at 3.1 mm the discs appear to be only 9 per cent smaller than when observed at 0.9 mm, in tension with models of dust evolution that predict a starker difference. Third, by forward modelling the sample of measurements with a simple parametric disc model, we find that the presence of large grains ($a_\mathrm{max}\gt 1\,$ mm) throughout the discs is the most favoured explanation for all discs as it reproduces simultaneously their spectral indices, optical depth, luminosity, and radial extent in the 0.9–1.3 mm wavelength range. We also find that the observations can be alternatively interpreted with the discs being dominated by optically thick, unresolved, substructures made of mm-sized grains with a high scattering albedo.
A type III-A CRISPR–Cas system mediates co-transcriptional DNA cleavage at the transcriptional bubbles in close proximity to active effectors
Authors: Lin Jinzhong , Shen Yulong , Ni Jinfeng , She Qunxin
Published: June 2021

Many type III CRISPR–Cas systems rely on the cyclic oligoadenylate (cOA) signaling pathway to exert immunization. However, LdCsm, a type III-A lactobacilli immune system mediates efficient plasmid clearance in spite of lacking cOA signaling. Thus, the system provides a good model for detailed characterization of the RNA-activated DNase in vitro and in vivo. We found ATP functions as a ligand to enhance the LdCsm ssDNase, and the ATP enhancement is essential for in vivo plasmid clearance. In vitro assays demonstrated LdCsm cleaved transcriptional bubbles at any positions in non-template strand, suggesting that DNA cleavage may occur for transcribing DNA. Destiny of target plasmid versus nontarget plasmid in Escherichia coli cells was investigated, and this revealed that the LdCsm effectors mediated co-transcriptional DNA cleavage to both target and nontarget plasmids, suggesting LdCsm effectors can mediate DNA cleavage to any transcriptional bubbles in close proximity upon activation. Subcellular locations of active LdCsm effectors were then manipulated by differential expression of LdCsm and CTR, and the data supported the hypothesis. Strikingly, stepwise induction experiments indicated allowing diffusion of LdCsm effector led to massive chromosomal DNA degradation, suggesting this unique IIIA system can facilitate infection abortion to eliminate virus-infected cells.
The effects of palbociclib in combination with radiation in preclinical models of aggressive meningioma
Authors: Horbinski Craig , Xi Guifa , Wang Yufen , Hashizume Rintaro , Gopalakrishnan Mahesh , Phillips Joanna J , Houghton Peter , James Charles D , Kalapurakal John A
Published: June 2021

Background

Meningiomas are the most common tumor arising within the cranium of adults. Despite surgical resection and radiotherapy, many meningiomas invade the brain, and many recur, often repeatedly. To date, no chemotherapy has proven effective against such tumors. Thus, there is an urgent need for chemotherapeutic options for treating meningiomas, especially those that enhance radiotherapy. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 that has been shown to enhance radiotherapy in preclinical models of other cancers, is well-tolerated in patients, and is used to treat malignancies elsewhere in the body. We, therefore, sought to determine its therapeutic potential in preclinical models of meningioma.

Methods

Patient-derived meningioma cells were tested in vitro and in vivo with combinations of palbociclib and radiation. Outputs included cell viability, apoptosis, clonogenicity, engrafted mouse survival, and analysis of engrafted tumor tissues after therapy.

Results

We found that palbociclib was highly potent against p16-deficient, Rb-intact CH157 and IOMM-Lee meningioma cells in vitro, but was ineffective against p16-intact, Rb-deficient SF8295 meningioma cells. Palbociclib also enhanced the in vitro efficacy of radiotherapy when used against p16-deficient meningioma, as indicated by cell viability and clonogenic assays. In vivo, the combination of palbociclib and radiation extended the survival of mice bearing orthotopic p16 deficient meningioma xenografts, relative to each as a monotherapy.

Conclusions

These data suggest that palbociclib could be repurposed to treat patients with p16-deficient, Rb-intact meningiomas, and that a clinical trial in combination with radiation therapy merits consideration.
Analysis of morphological characteristics of IDH-mutant/wildtype brain tumors using whole-lesion phenotype analysis
Authors: Snyder James M , Huang Raymond Y , Bai Harrison , Rao Vikram R , Cornes Susannah , Barnholtz-Sloan Jill S , Gutman David , Fasano Rebecca , Van Meir Erwin G , Brat Daniel , Eschbacher Jennifer , Quackenbush John , Wen Patrick Y , Lee Jong Woo
Published: June 2021

Background

Although IDH-mutant tumors aggregate to the frontotemporal regions, the clustering pattern of IDH-wildtype tumors is less clear. As voxel-based lesion-symptom mapping (VLSM) has several limitations for solid lesion mapping, a new technique, whole-lesion phenotype analysis (WLPA), is developed. We utilize WLPA to assess spatial clustering of tumors with IDH mutation from The Cancer Genome Atlas and The Cancer Imaging Archive.

Methods

The degree of tumor clustering segmented from T1 weighted images is measured to every other tumor by a function of lesion similarity to each other via the Hausdorff distance. Each tumor is ranked according to the degree to which its neighboring tumors show identical phenotypes, and through a permutation technique, significant tumors are determined. VLSM was applied through a previously described method.

Results

A total of 244 patients of mixed-grade gliomas (WHO II–IV) are analyzed, of which 150 were IDH-wildtype and 139 were glioblastomas. VLSM identifies frontal lobe regions that are more likely associated with the presence of IDH mutation but no regions where IDH-wildtype was more likely to be present. WLPA identifies both IDH-mutant and -wildtype tumors exhibit statistically significant spatial clustering.

Conclusion

WLPA may provide additional statistical power when compared with VLSM without making several potentially erroneous assumptions. WLPA identifies tumors most likely to exhibit particular phenotypes, rather than producing anatomical maps, and may be used in conjunction with VLSM to understand the relationship between tumor morphology and biologically relevant tumor phenotypes.
Successful Treatment of Persistent Coronavirus Disease 2019 Infection in a Patient With Hypogammaglobulinemia With REGN-COV2: A Case Report
Authors: Luitel Pankaj , Vais Dana , Gidron Adi
Published: June 2021

A 55-year-old man with hypogammaglobulinemia due to previous rituximab treatment developed persistent coronavirus disease 2019 pneumonia. Treatment with REGN-COV2 (casirivimab and imdevimab) resulted in the clearance of the infection. Targeted antiviral antibodies may be an important weapon in the management of immunocompromised patients infected with severe acute respiratory syndrome coronavirus 2 who fail to mount an immune response.
Sea ice and local weather affect reproductive phenology of a polar seabird with breeding consequences
Authors: Sauser Christophe , Delord Karine , Barbraud Christophe
Published: June 2021

Breeding at the right time is essential for animals living in seasonal environments to ensure that energy requirements for reproduction, especially the nutritional needs for rearing offspring, coincide with peak food availability. Climate change is likely to cause modifications in the timing of maximum food availability, and organisms living in polar environments where the breeding period is heavily contracted may be particularly affected. Here we used a 26-year dataset to study the phenological response of a pagophilic species, the Snow Petrel (Pagodroma nivea), to climate change and its demographic impact. First, we investigated the trends and relationships between climate variables and hatching dates measured in three neighboring colonies. In a second step, we examined the impact of the hatching date and environmental covariates on the fledging probability. Our results showed that sea ice, a climate-related variable, showed a positive temporal trend. We found that hatching date was delayed when sea ice concentration was greater and local weather conditions were worse (i.e., increase in the number of windy days or the number of snow days). Hatching date had a negative effect on fledging probability, and fledging probability showed a bell-shaped temporal trend. We suggest that Snow Petrels can delay breeding phenology in response to environmental conditions. However, this plasticity may be limited as fledging success decreased with delayed hatching, potentially making the Snow Petrel vulnerable to a mismatch between resource availability and nutritional needs.
Experiences of Patient-Led Chronic Pain Peer Support Groups After Pain Management Programs: A Qualitative Study
Authors: Farr Michelle , Brant Heather , Patel Rita , Linton Myles-Jay , Ambler Nicholas , Vyas Sareeta , Wedge Hannah , Watkins Sue , Horwood Jeremy
Published: June 2021

Objective

A qualitative study of patients’ experiences and the impacts of peer support groups that patients maintained after UK NHS group pain management programs (PMPs).

Design

Long-term impacts of group PMPs remain unclear, with indications that positive effects can fade. We evaluated a model of continued peer support, co-produced by patients and clinicians, to maintain the therapeutic impact of PMP groups. A protocol was implemented that encouraged patients to continue to meet in their established PMP group for patient-led peer support (without clinical input) after PMPs finished. Peer support aimed to consolidate self-management, and advance social life recovery. We examined the impacts that groups had on attendees, and why some dropped out.

Methods

Semi-structured interviews with 38 patients and 7 clinicians, analyzed thematically.

Results

Friendship bonds and mutual understandings of effective ways of coping with pain encouraged participants to maintain recovery following PMPs. After PMP professional involvement has ended, these meetings enabled patients to develop greater agency from the shared sense of helping bring about new achievements or averting setbacks. Peer support extended the understanding of what is possible when living with pain. However, continuing meetings were not right for all. Reasons for not attending included lack of connection with peers.

Conclusions

Co-produced peer support groups after PMPs can be a low-cost, effective social intervention, providing emotional, practical and social benefits, with improved self-management skills, stronger social connections and some reduced use of health services. Project resources for developing peer support meetings after PMPs are freely available online.
Balancing the Deontological and Utilitarian Values of Inter-Institutional Management: The Case of Urban Policing
Authors: Yuval Fany , Porat Irit
Published: June 2021

Inter-institutional management struggles to balance the deontological and utilitarian values of public services. Urban policing exemplifies this subtle balance between the different yet complementary authorities and tools entrusted to municipalities and the police to ensure personal and environmental safety, and tackle the nuisances that negatively impact residents’ quality of life. Hence, democracies adopt different approaches to managing the interplay between municipalities and the police. Integrating the public value accounting, strategic triangle, and PerformanceStat approaches, we analyse the effective inter-institutional management of the local authorities and the police using three models of urban policing that currently exist in Israel. Based on in-depth interviews, we suggest an improved strategy that balances deontological and utilitarian values, and should result in financial savings, less need to use authority and force, sensitive enforcement services, and value for local residents.