bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-200b-mediated reversion of a spectrum of epithelial-to-mesenchymal transition states in recessive dystrophic epidermolysis bullosa squamous cell carcinomas
Authors: Illmer Julia , Zauner Roland , Piñón Hofbauer Josefina , Wimmer Monika , Gruner Stefanie , Ablinger Michael , Bischof Johannes , Dorfer Sonja , Hainzl Stefan , Tober Vanessa , Bergson Shir , Sarig Ofer , Samuelov Liat , Guttmann-Gruber Christina , Shalom-Feuerstein Ruby , Sprecher Eli , Koller Ulrich , Laimer Martin , Bauer Johann W , Wally Verena 
Published: September 2023

Abstract

Background
Cutaneous squamous cell carcinoma (SCC) is the leading cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). However, the survival time from first diagnosis differs between patients; some tumours spread particularly fast, while others may remain localized for years. As treatment options are limited, there is an urgent need for further insights into the pathomechanisms of RDEB tumours, to foster therapy development and support clinical decision-making.

Objectives
To investigate differences in RDEB tumours of diverging aggressiveness at the molecular and phenotypic level, with a particular focus on epithelial-to-mesenchymal (EMT) transition states and thus microRNA-200b (miR-200b) as a regulator.

Methods
Primary RDEB-SCC keratinocyte lines were characterized with respect to their EMT state. For this purpose, cell morphology was classified and the expression of EMT markers analysed using immunofluorescence, flow cytometry, semi-quantitative reverse transcriptase polymerase chain reaction and Western blotting. The motility of RDEB-SCC cells was determined and conditioned medium of RDEB-SCC cells was used to treat endothelial cells in an angiogenesis assay. In addition, we mined previously generated microRNA (miRNA) profiling data to identify a candidate with potential therapeutic relevance and performed transient miRNA transfection studies to investigate the candidate’s ability to reverse EMT characteristics.

Results
We observed high variability in EMT state in the RDEB-SCC cell lines, which correlated with in situ analysis of two available patient biopsies and respective clinical disease course. Furthermore, we identified miR-200b-3p to be downregulated in RDEB-SCCs, and the extent of deregulation significantly correlated with the EMT features of the various tumour lines. miR-200b-3p was reintroduced into RDEB-SCC cell lines with pronounced EMT features, which resulted in a significant increase in epithelial characteristics, including cell morphology, EMT marker expression, migration and angiogenic potential.

Conclusions
RDEB-SCCs exist in different EMT states and the level of miR-200b is indicative of how far an RDEB-SCC has gone down the EMT path. Moreover, the reintroduction of miR-200b significantly reduced mesenchymal features.
Associations of calcium, phosphate and intact parathyroid hormone levels with mortality, residual kidney function and technical failure among patients on peritoneal dialysis
Authors: Murashima Miho , Fujii Naohiko , Goto Shunsuke , Hasegawa Takeshi , Abe Masanori , Hanafusa Norio , Fukagawa Masafumi , Hamano Takayuki 
Published: September 2023

ABSTRACT

Background
Associations of calcium, phosphate and intact parathyroid hormone (iPTH) levels with outcomes may be different between patients on peritoneal dialysis (PD) and hemodialysis (HD). The aim of the study is to evaluate these associations among PD patients.

Methods
In this prospective cohort study on the Japan Renal Data Registry, adults on PD at the end of 2009 were included. The observation period was until the end of 2018 and the data were censored at the time of transplantation or transition to HD. Exposures were time-averaged or time-dependent albumin-corrected calcium (cCa), phosphate and iPTH levels. Outcomes were all-cause and cardiovascular mortality, transition to HD and urine output. Data were analyzed using Cox regression models or linear mixed-effects models and the results were shown as cubic spline curves.

Results
Among 7393 patients, 590 deaths and 211 cardiovascular deaths were observed during a median follow-up of 3.0 years. Higher cCa and phosphate levels were associated with higher mortality. Lower cCa levels were associated with a faster decline, whereas lower phosphate was associated with a slower decline in urine output. Lower phosphate and iPTH levels were associated with a lower incidence of transition to HD.

Conclusions
Among PD patients, the observed associations of cCa, phosphate and iPTH with mortality, residual kidney function and technical failure suggest that avoiding high cCa, phosphate and iPTH levels might improve outcomes.
What eyes do not see the heart does not grieve over? The role of intracoronary imaging in acute myocardial infarction: a case report
Authors: Blasco-Turrión Sara , Gómez-López Andrea , Morales-Ponce Francisco J , Casquero-Domínguez Sara , del Pozo-Contreras Rocío 
Published: September 2023

Abstract

Background
The evaluation of a three-dimensional structure with a two-dimensional imaging technique makes intracoronary diagnostic techniques essential, especially in the setting of acute myocardial infarction (AMI) when no apparent coronary lesions are detected. Expert consensus recommend their use in certain scenarios such as angiographically ambiguous disease and identification of the culprit lesion. Although both intravascular ultrasound and optical coherence tomography (OCT) allow the characterization of the atherosclerotic plaque and assess the immediate and long-term results of stent implantation, they have their own benefits and limitations that make them ideal for different types of coronary lesions.

Case summary
We present the case of a lateral ST-elevation myocardial infarction with no evident coronary lesions in angiography, in which OCT not only allowed us to confirm a diagonal branch occlusion, but it also became crucial to locate the occlusion point and to guide the procedure, allowing complete revascularization of the culprit lesion that otherwise could have been missed.

Discussion
To know the actual limitations of conventional coronary angiography to adequately assess coronary disease, intracoronary diagnostic techniques are key to evaluate the underlying mechanisms of the event, especially in the setting of AMI when no clear culprit lesion has been identified. They can be of great value to locate and revascularize acute occlusions that could go unnoticed on the angiogram, guiding the revascularization and stent implantation and, therefore, preventing myocardial injury that could become irreversible when coronary disease is not treated promptly.
Workforce affiliation in primary and secondary prevention implantable cardioverter defibrillator patients: a nationwide Danish study
Authors: Rosenkranz Simone H , Wichmand Charlotte H , Smedegaard Lærke , Møller Sidsel , Bjerre Jenny , Schou Morten , Torp-Pedersen Christian , Philbert Berit T , Larroudé Charlotte , Melchior Thomas M , Nielsen Jens C , Johansen Jens B , Riahi Sam , Holmberg Teresa , Gislason Gunnar , Ruwald Anne-Christine 
Published: September 2023

Abstract

Background and aim
There are a paucity of studies investigating workforce affiliation in connection with first-time implantable cardioverter defibrillator (ICD)-implantation. This study explored workforce affiliation and risk markers associated with not returning to work in patients with ICDs.

Methods
Using the nationwide Danish registers, patients with a first-time ICD-implantation between 2007 and 2017 and of working age (30–65 years) were identified. Descriptive statistic and logistic regression models were used to describe workforce affiliation and to estimate risk markers associated with not returning to work, respectively. All analyses were stratified by indication for implantation (primary and secondary prevention).

Results
Of the 4659 ICD-patients of working age, 3300 patients (71%) were members of the workforce (employed, on sick leave or unemployed) (primary: 1428 (43%); secondary:1872 (57%)). At baseline, 842 primary and 1477 secondary prevention ICD-patients were employed. Of those employed at baseline, 81% primary and 75% secondary prevention ICD-patients returned to work within 1 year, whereof more than 80% remained employed the following year. Among patients receiving sick leave benefits at baseline, 25% were employed after 1 year. Risk markers of not returning to work were ‘younger age’ in primary prevention ICD-patients, while ‘female sex’, left ventricular ejection fraction ‘LVEF ≤40’, ‘lower income’, and ‘≥3 comorbidities’ were risk markers in secondary prevention ICD-patients. Lower educational level was a risk marker in both patient groups.

Conclusion
High return-to-work proportions following ICD-implantation, with a subsequent high level of employment maintenance were found. Several significant risk markers of not returning to work were identified including ‘lower educational level’ that posed a risk in both patient groups.

Trial registration number
Capital Region of Denmark, P-2019-051.
Genome-wide methylation patterns from canine nanopore assemblies
Authors: Schall Peter Z , Winkler Paige A , Petersen-Jones Simon M , Yuzbasiyan-Gurkan Vilma , Kidd Jeffrey M 
Published: September 2023

Abstract
Recent advances in long-read sequencing have enabled the creation of reference-quality genome assemblies for multiple individuals within a species. In particular, 8 long-read genome assemblies have recently been published for the canine model (dogs and wolves). These assemblies were created using a range of sequencing and computational approaches, with only limited comparisons described among subsets of the assemblies. Here we present 3 high-quality de novo reference assemblies based upon Oxford Nanopore long-read sequencing: 2 Bernese Mountain Dogs (BD & OD) and a Cairn terrier (CA611). These breeds are of particular interest due to the enrichment of unresolved genetic disorders. Leveraging advancement in software technologies, we utilized published data of Labrador Retriever (Yella) to generate a new assembly, resulting in a ∼280-fold increase in continuity (N50 size of 91 kbp vs 25.75 Mbp). In conjunction with these 4 new assemblies, we uniformly assessed 8 existing assemblies for generalized quality metrics, sequence divergence, and a detailed BUSCO assessment. We identified a set of ∼400 conserved genes during the BUSCO analysis missing in all assemblies. Genome-wide methylation profiles were generated from the nanopore sequencing, resulting in broad concordance with existing whole-genome and reduced-representation bisulfite sequencing, while highlighting superior overage of mobile elements. These analyses demonstrate the ability of Nanopore sequencing to resolve the sequence and epigenetic profile of canine genomes.
Is employment group insurance financing of expensive gene therapies threatened in the United States?
Authors: Doshi Jalpa A , Eilers Morgan , Gupta Atul , Pauly Mark , Olssen Alexander L 
Published: September 2023

Abstract
Despite the potential of gene therapy to transform the lives of patients with rare genetic diseases, serious concern has been raised about the financing of the high up-front costs for such treatments and about the ability of the employer-sponsored insurance system in the United States, particularly in small firms, to pay for discoveries of this type. In this paper, we provide a conceptual framework and empirical evidence to support the proposition that, at present, private group insurance financing of cost-effective gene therapies is not only feasible and competitively necessary in the labor market for employers, regardless of group size, but also that, currently, the number of US workers in small firms who might be stressed by very high-priced claims is a tiny fraction of the group market for genetic treatments. The current system of employer-paid self-insurance supplemented by stop-loss coverage should be able to facilitate the use of new cost-effective gene therapies. Other alternative methods of financing that have been proposed may not be urgently needed. There are, however, some concerns about the long-term resilience of this system if stop-loss premiums continue to have high growth.
MaMADS1–MaNAC083 transcriptional regulatory cascade regulates ethylene biosynthesis during banana fruit ripening
Authors: Wei Wei , Yang Ying-ying , Wu Chao-jie , Kuang Jian-fei , Chen Jian-ye , Lu Wang-jin , Shan Wei 
Published: September 2023

Abstract
The hormone ethylene is crucial in the regulation of ripening in climacteric fruit, such as bananas. The transcriptional regulation of ethylene biosynthesis throughout banana fruit ripening has received much study, but the cascaded transcriptional machinery of upstream transcriptional regulators implicated in the ethylene biosynthesis pathway is still poorly understood. Here we report that ethylene biosynthesis genes, including MaACS1, MaACO1, MaACO4, MaACO5, and MaACO8, were upregulated in ripening bananas. NAC (NAM, ATAF, CUC) transcription factor, MaNAC083, a ripening and ethylene-inhibited gene, was discovered as a potential binding protein to the MaACS1 promoter by yeast one-hybrid screening. Further in vitro and in vivo experiments indicated that MaNAC083 bound directly to promoters of the five ethylene biosynthesis genes, thereby transcriptionally repressing their expression, which was further verified by transient overexpression experiments, where ethylene production was inhibited through MaNAC083-modulated transcriptional repression of ethylene biosynthesis genes in banana fruits. Strikingly, MaMADS1, a ripening-induced MADS (MCM1, AGAMOUS, DEFICIENS, SRF4) transcription factor, was found to directly repress the expression of MaNAC083, inhibiting trans-repression of MaNAC083 to ethylene biosynthesis genes, thereby attenuating MaNAC083-repressed ethylene production in bananas. These findings collectively illustrated the mechanistic basis of a MaMADS1–MaNAC083–MaACS1/MaACOs regulatory cascade controlling ethylene biosynthesis during banana fruit ripening. These findings increase our knowledge of the transcriptional regulatory mechanisms of ethylene biosynthesis at the transcriptional level and are expected to help develop molecular approaches to control ripening and improve fruit storability.
Trends in larval densities, spawning timing, and site quality of capelin (Mallotus villosus) across bays and habitats in Newfoundland, Canada
Authors: Tripp A , Murphy H M , Penton P M , Davoren G K 
Published: September 2023

Abstract
Capelin is a short-lived forage fish species that underwent a population collapse in 1991 on the Newfoundland and Labrador Shelf, Canada (Northwest Atlantic Fisheries Organization Divisions 2J3KL) and has not recovered. The collapsed stock is characterized by delayed spawning timing and low recruitment. As year-class strength is set early in life, long-term larval monitoring at an intertidal spawning site in Trinity Bay (TB) is used as a proxy for stock-wide recruitment. Capelin spawn at both intertidal and subtidal habitats; however, there is minimal larval information from bays with a high incidence of subtidal spawning. We aimed to (i) compare inter-annual trends in temperatures, timing of spawning, and annual larval densities between two northeastern bays [TB and Notre Dame Bay (NDB)] and (ii) compare habitat quality metrics and larval densities between subtidal and intertidal sites in NDB. The date of first spawning in TB and NDB was positively correlated, suggesting that years with delayed spawning are experienced shelf-wide. While larval density was lower in NDB compared to TB, inter-annual trends were similar. In NDB, larval densities at both intertidal and subtidal spawning habitats were similar within a year, but temperatures and the proportion of dead eggs were lower at subtidal sites. These habitat quality metrics, however, were not related to annual larval density. These findings improve our knowledge on sources of capelin productivity, including the potential importance of subtidal spawning to recruitment dynamics.
Using Climate Litigation to Strengthen Advocacy Strategies: The Life After Coal Campaign in South Africa
Authors: Chamberlain Lisa , Fourie Melissa 
Published: September 2023

AbstractActivists in South Africa have a long history of using public interest litigation to realize human rights. The use of litigation is nevertheless contested and has produced rich scholarship exploring how its impact can be understood. This practice note will examine the use of litigation by the Life After Coal campaign in Earthlife Africa Johannesburg v. Minister of Environmental Affairs 2017, 2 All SA 519 (GP) (Thabametsi case). With the ultimate goal of reducing greenhouse gas emissions, Life After Coal has been campaigning since 2015 to thwart investment in new coal-fired power in South Africa. They successfully used the Thabametsi case to strengthen the use of a variety of other strategies, including protest, media advocacy, economic modelling, and pressure on investors and financial institutions. Although litigation can be painfully slow and resource intensive, in this campaign it was instrumental. Litigation delayed the regulatory approvals required for commercial close. While this was not the purpose of the litigation, its effect was to delay the flow of funds and the start of construction on the project. This in turn created time and space for an advocacy campaign to persuade financiers and investors to withdraw their backing for the project; to undertake the modelling and research required to back up the advocacy campaigns and litigation; and for clean renewable energy to become cheap enough to present a viable alternative pathway to coal. This practice note documents this rare success story and suggests what lessons concerning the use of multiple interweaving strategies it provides for climate activists in the global South.
SV2B defines a subpopulation of synaptic vesicles
Authors: Paulussen Isabelle , Beckert Hannes , Musial Timothy F , Gschossmann Lena J , Wolf Julia , Schmitt Mathieu , Clasadonte Jérôme , Mairet-Coello Georges , Wolff Christian , Schoch Susanne , Dietrich Dirk 
Published: September 2023

Abstract
Synaptic vesicles can undergo several modes of exocytosis, endocytosis, and trafficking within individual synapses, and their fates may be linked to different vesicular protein compositions. Here, we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron microscopy. SV2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active zone. In contrast, SV2A was found in all domains of the synapse and was slightly enriched near the active zone. SV2B and SV2A were found on the membrane in the peri-active zone, suggesting the recycling from both clusters of vesicles. SV2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency stimulation. Our data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial gradients. The almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found more important for vesicle release.
Maturation of metastases in peripheral neuroblastic tumors (neuroblastoma) of children
Authors: Sarnat Harvey B , Chan Elaine S , Ng Denise , Yu Weiming 
Published: September 2023

Abstract
Peripheral neuroblastic tumors of childhood exhibit 3 principal neural crest lineages: primitive neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. They are unique in undergoing maturation of neurons (ganglion cells) and Schwann cells, thereby recapitulating normal fetal neuronal development in the brain. Precision in estimating neurogenesis is enhanced by immunoreactivities of markers of neuronal maturation. Whether organ tissue factors in different sites of metastases influence rates of maturation and whether metastases are similar to their primary neuroblastic tumor are incompletely documented. Four young children, 1 with a mixed primary adrenal tumor and 3 with metastases were studied at surgery or autopsy. Immunocytochemical reactivities included microtubule-associated protein-2, synaptophysin, chromogranin-A, somatostatin, keratan sulfate, vimentin, S-100β protein, and PHOX2B. Primary tumors were non-uniform with regions of either poor or enhanced maturation. Both neuronal and Schwannian lineages were represented in each tumor type but differed in proportions. Bi- or multi-nucleated ganglion cells matured equal to mononuclear forms. Ganglion cell maturation was similar in metastases regardless of the target organ. Metastases resembled primary tumors. Immunocytochemical markers of neuronal and of Schwann cell maturation provide greater diagnostic precision to supplement histological criteria. Interval between diagnosis of primary tumor and metastases, metastatic target tissues, and chemotherapy over an interval of time do not appear to influence neuroblastic or Schwann cell differentiation.
Associations of Standard Care, Intrathecal Antibiotics, and Antibiotic-Impregnated Catheters With Cerebrospinal Fluid Shunt Infection Organisms and Resistance
Authors: Sedano Sabrina , Kronman Matthew P , Whitlock Kathryn B , Zhou Chuan , Coffin Susan E , Hauptman Jason S , Heller Evan , Mangano Francesco T , Pollack Ian F , Schaffzin Joshua K , Thorell Emily , Warf Benjamin C , Simon Tamara D 
Published: September 2023

Abstract

Background
Infection prevention techniques used during cerebrospinal fluid (CSF) shunt surgery include: (1) standard perioperative intravenous antibiotics, (2) intrathecal (IT) antibiotics, (3) antibiotic-impregnated catheter (AIC) shunt tubing, or (4) Both IT and AIC. These techniques have not been assessed against one another for their impact on the infecting organisms and patterns of antimicrobial resistance.

Methods
We performed a retrospective longitudinal observational cohort study of children with initial CSF shunt placement between January 2007 and December 2012 at 6 US hospitals. Data were collected electronically from the Pediatric Health Information Systems+ (PHIS+) database, and augmented with standardized chart review. Only subjects with positive CSF cultures were included in this study.

Results
Of 1,723 children whose initial shunt placement occurred during the study period, 196 (11%) developed infection, with 157 (80%) having positive CSF cultures. Of these 157 subjects, 69 (44%) received standard care, 28 (18%) received AIC, 55 (35%) received IT antibiotics, and 5 (3%) received Both at the preceding surgery. The most common organisms involved in monomicrobial infections were Staphylococcus aureus (38, 24%), coagulase-negative staphylococci (36, 23%), and Cutibacterium acnes (6, 4%). Compared with standard care, the other infection prevention techniques were not significantly associated with changes to infecting organisms; AIC was associated with decreased odds of methicillin resistance among coagulase-negative staphylococci.

Conclusions
Because no association was found between infection prevention technique and infecting organisms when compared to standard care, other considerations such as tolerability, availability, and cost should inform decisions about infection prevention during CSF shunt placement surgery.
A Review of Pediatric Central Line-Associated Bloodstream Infections Reported to the National Healthcare Safety Network: United States, 2016–2022
Authors: Prestel Christopher , Fike Lucy , Patel Prachi , Dudeck Margaret , Edwards Jonathan , Sinkowitz-Cochran Ronda , Kuhar David 
Published: September 2023

Abstract
Central line-associated bloodstream infections (CLABSIs) are common healthcare-associated infections in pediatrics. Children’s hospital CLABSI standardized infection ratios decreased when comparing 2016–2019 (−26%, 95% CI [−31%, −20%]), and increased from 2019 to 2022 (18%, 95% CI [9%, 26%]). Resilient pediatric CLABSI prevention initiatives are needed.