bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative Risk Assessment of Ecological Areas with the Highest Potential Impact of Underwater Released Exhaust CO2 from Innovative Ships
Authors: Wei Yuzhu , Kroeze Michel , Vámos Csilla , Foekema Edwin M. , van Lammeren Ron , Murk Albertinka J. 
Published: October 2021

AbstractApplying underwater released exhaust gas as ‘air lubrication’ along the ship’s hull to reduce the energy consumption is under development. However, this direct emission to the water could pose a risk to the local marine environment, especially in shipping-dense areas. Specifically, CO2, a dominant component in the exhaust gas, has the potency to enhance algal blooms and cause acidification. This study provides the first relative risk assessment of ships with underwater release exhaust gas systems on a global scale, taking into account local water conditions and shipping intensity. Risk was characterized for 262 marine ecoregions by plotting the expected CO2 emission from ships to water against the estimated vulnerability to acidification and algal blooms. The vulnerability of each ecoregion was assessed based on background dissolved inorganic carbon (DIC) level, chlorophyll-a concentrations and total alkalinity. The results reveal that areas with relatively high vulnerability are mainly located above 30° N latitude. The Yellow Sea, Southern China Sea, and North Sea come out as relatively high risk areas. Looking in more detail to European high-risk ecoregions, the highest risk levels are found in areas with dense shipping lanes and maritime chokepoints, e.g. the Strait of Dover and the Strait of Gibraltar. This was the first attempt to make such a risk assessment and the outcome is only indicative. In a next phase additional parameters, such as water currents and biological composition of the ecosystem should be included.Key PointsThe first global environmental risk assessment was made for innovative ships that apply underwater released exhaust gas as ‘air lubrication’Ecoregions with relatively high vulnerability to acidification and algal blooms are mainly located above 30° N latitudeThe risk for the marine ecosystem of the underwater released exhaust CO2 from ships is limited to specific shipping-dense areas
Efficient methods for generation and expansion of, and gene delivery to Rhesus Macaque plasma B cells
Authors: Kreuser Shannon , Honaker Yuchi , Cheng Rene Yu-Hong , Dahl Noelle , Soligalla Rupa , Lopez Christina , Rawlings David J. , James Richard G. 
Published: October 2021

ABSTRACTEngineered long lived plasma cells have the potential to be a new area of cell therapy. A key step in developing this cell therapy is testing in a model with an intact immune system similar to humans. To that end, we have developed methods to purify, expand, and differentiate non-human primate (NHP; rhesus macaque) B cells ex vivo. By comparing several media types and conditions, we consistently achieved 10-fold expansion of NHP B cells using a readily available commercial supplement. After only seven days in culture, large percentages of cells in NHP B cell cultures were differentiated. These cells expressed surface markers found in human antibody secreting cells (CD38 and CD138) and secreted immunoglobulin G. We also identified the serotypes (2.5 and D-J) and conditions necessary for efficient transduction of NHP B cells with AAV vectors for the purposes of producing a secreted protein (BAFF). We hope that this work will accelerate proof-of-concept in vivo studies using engineered protein-secreting B cells in an NHP model.
Cortical sensorimotor activity in the execution and suppression of discrete and rhythmic movements
Authors: Hervault Mario , Zanone Pier–Giorgio , Buisson Jean–Christophe , Huys Raoul 
Published: October 2021

AbstractAlthough the engagement of sensorimotor cortices in movement is well documented, the functional relevance of brain activity patterns remains ambiguous. Especially, the cortical engagement specific to the pre-, within-, and post-movement periods is poorly understood. The present study addressed this issue by examining sensorimotor EEG activity during the performance as well as STOP-signal cued suppression of movements pertaining to two distinct classes, namely, discrete vs. ongoing rhythmic movements. Our findings indicate that the lateralized readiness potential (LRP), which is classically used as a marker of pre-movement processing, indexes multiple pre- and in-movement-related brain dynamics in a movement-class dependent fashion. In- and post-movement event-related (de)synchronization (ERD/ERS) observed in the Mu (8-13 Hz) and Beta (15-30 Hz) frequency ranges were associated with estimated brain sources in both motor and somatosensory cortical areas. Notwithstanding, Beta ERS occurred earlier following cancelled than actually performed movements. In contrast, Mu power did not vary. Whereas Beta power may reflect the evaluation of the sensory predicted outcome, Mu power might engage in linking perception to action. Additionally, the rhythmic movement forced stop (only) showed a post-movement Mu/Beta rebound, which might reflect an active “clearing-out” of the motor plan and its feedback-based online control. Overall, the present study supports the notion that sensorimotor EEG modulations are key markers to investigate control or executive processes, here initiation and inhibition, which are exerted when performing distinct movement classes.
Bacillus subtilis with a 1% population enhances the activity of Enterococcus faecalis with a 99% population
Authors: Ito Tsukasa , Yamanashi Yu 
Published: October 2021

ABSTRACTMicrobes are present as communities in the environment. However, the importance of minor populations has not been well studied experimentally. In this study, we evaluated the role of Bacillus subtilis with a 1% population and its effect on co-incubated Enterococcus faecalis with a 99% population. Here we used an azo dye-decolorizing Enterococcus faecalis strain T6a1 and non-dye-decolorizing Bacillus subtilis strain S4ga. The dye decolorization assay enabled the investigation of the effects of B. subtilis S4ga on the activity of E. faecalis T6a1, even when B. subtilis S4ga was present at only 1% relative abundance or lower. We found that non-decolorizing B. subtilis S4ga enhanced the dye decolorization activity of E. faecalis T6a1, shortened the lag time of E. faecalis T6a1 to start decreasing the dye concentration, and increased the time for E. faecalis T6a1 to continue dye decolorization. These effects were correlated with redox potential values. We compared the extracellular amino acids between each incubation culture of E. faecalis T6a1 and B. subtilis S4ga, which revealed their mutual relationship by cross-feeding of specific amino acids. We also compared the intracellular primary metabolites between co-incubation and sole incubation of E. faecalis T6a1. The arginine deiminase (ADI) pathway in the co-incubated E. faecalis T6a1 was activated compared to that of E. faecalis T6a1 incubated solely. These findings explained that co-incubation with B. subtilis S4ga promoted ATP production in E. faecalis T6a1 cells to a greater extent and enhanced dye-decolorization activity.IMPORTANCEThis study highlights the importance of minor bacterial populations and their effects on major populations. We used Enterococcus faecalis as the major population and Bacillus subtilis as the minor population. Both species are becoming increasingly important. Some strains of E. faecalis are antibiotic-resistant pathogens, show probiotic effects, or are applicable for textile wastewater treatment. Some strains of B. subtilis are known to produce antimicrobial agents, reduce intestinal inflammation, or restore gut microbiota. We demonstrated that a low abundance of B. subtilis with 1% population increased the amount of energy produced by E. faecalis with 99% population, which appeared as enhanced dye decolorization activity of dye-decolorizing E. faecalis. Metabolomic analysis suggested that E. faecalis and B. subtilis had a mutual relationship by feeding specific amino acids to each other. These results provide new insights into co-existing minor populations in microbial communities and will improve our understanding of bacterial control.Graphical abstract
Longitudinal SARS-CoV-2 testing is punctuated by intermittent positivity and variable rates of cycle-threshold decline
Authors: Hawken Shawn E. , Sellers Subhashini A. , Smedberg Jason R. , Ward Jeremy D. , Whinna Herbert C. , Fischer William , Miller Melissa B. 
Published: October 2021

AbstractThe COVID-19 pandemic is complicated by cases of vaccine-breakthrough, re-infection, and widespread transmission of variants of concern (VOC). Consequently, the need to interpret longitudinal positive SARS-CoV-2 (SCV-2) tests is crucial in guiding clinical decisions regarding infection control precautions and treatment. Although quantitative tests are not routinely used diagnostically, standard diagnostic RT-PCR tests yield Ct values that are inversely correlated with RNA quantity. In this study, we performed a retrospective review of 72,217 SCV-2 PCR positive tests and identified 264 patients with longitudinal positivity prior to vaccination and VOC circulation. Patients with longitudinal positivity fell into two categories: short-term (207, 78%) or prolonged (57, 22%) positivity, defined as <= 28 (range 1-28, median 16) days and >28 (range 29-152, median 41) days, respectively. In general, Ct values declined over time in both groups; however, 11 short-term positive patients had greater amounts of RNA detected at their terminal test compared to the first positive, and 5 patients had RNA detected at Ct < 35 at least 40 days after initial infection. Oscillating positive and negative results occurred in both groups, although oscillation was seen three times more frequently in prolonged-positive patients. Patients with prolonged positivity had diverse clinical characteristics but were often critically ill and were discharged to high-level care or deceased (22%). Overall, this study demonstrates that caution must be emphasized when interpreting Ct values as a proxy for infectivity, predictor of severity, or a guide for patient care decisions in the absence of additional clinical context.
ASIP promoter variants predict sesame coat color in Shiba Inu dogs
Authors: Belyakin S.N , Maksimov D.A. , Pobedintseva M.A. , Laktionov P.P. , Voronova D. 
Published: October 2021

AbstractDifferent patterns of coat color pigmentation in dogs are produced by a sophisticated interaction of several genes. Understanding the mechanisms underlying the diversity of coat colors and their inheritance is important for professional breeders because it helps to predict the phenotypes of the progeny. Although genetics of the main coat colors in dogs is extensively studied, there are types of coat pigmentation that are not explained yet. Recently a new model connected the variants in ASIP gene promoters with different coat colors in dogs. Here we used this model as a framework to investigate the genetics of the rare sesame coat color in Shiba Inu dogs. We determined the combination of two alleles of ASIP gene that determine sesame coat color. This finding can be used by the breeders to produce the dogs with this rare coat color pattern. We also demonstrate the incomplete dominance between the ASIP alleles involved in sesame coat formation. These results are in good agreement with the new model explaining how different levels of ASIP gene expression affect the regulation of pigment synthesis in melanocytes.
Rad24-RFC loads the 9-1-1 clamp by inserting DNA from the top of a wide-open ring, opposite the mechanism of RFC/PCNA
Authors: Zheng Fengwei , Georgescu Roxana E. , Yao Nina Y. , O’Donnell Michael E. , Li Huilin 
Published: October 2021

ABSTRACTIn response to DNA damage, the ring-shaped 9-1-1 clamp is loaded onto 5’ recessed DNA to arrest the cell cycle and activate the DNA damage checkpoint. The 9-1-1 clamp is a heterotrimeric ring that is loaded in S. cerevisiae by Rad24-RFC, an alternative clamp loader in which Rad24 replaces the Rfc1 subunit in the RFC1-5 clamp loader of PCNA. Unlike RFC that loads the PCNA ring onto a 3’-ss/ds DNA junction, Rad24-RFC loads the 9-1-1 ring onto a 5’-ss/ds DNA junction, a consequence of DNA damage. The underlying 9-1-1 clamp loading mechanism has been a mystery. Here we report two 3.2-Å cryo-EM structures of Rad24-RFC bound to DNA and either a closed or 27 Å open 9-1-1 clamp. The structures reveal a completely unexpected mechanism by which a clamp can be loaded onto DNA. The Rad24 subunit specifically recognizes the 5’-DNA junction and holds ds DNA outside the clamp loader and above the plane of the 9-1-1 ring, rather than holding DNA inside and below the clamp as in RFC. The 3’ ssDNA overhang is required to obtain the structure, and thus confers a second DNA binding site. The bipartite DNA binding by Rad24-RFC suggests that ssDNA may be flipped into the open 9-1-1 ring, similar to ORC-Cdc6 that loads the Mcm2-7 ring on DNA. We propose that entry of ssDNA through the 9-1-1 ring triggers the ATP hydrolysis and release of the Rad24-RFC. The key DNA binding residues are conserved in higher eukaryotes, and thus the 9-1-1 clamp loading mechanism likely generalizes.
ERK signaling dissolves ERF Repression Condensates in Living Embryos
Authors: Weaver Claire J. , Patel Aleena L. , Shvartsman Stanislav Y. , Levine Michael S. , Treen Nicholas 
Published: October 2021

ABSTRACTPhase separation underlies the organization of the nucleus, including the biogenesis of nucleoli and the packaging of heterochromatin. Here we explore the regulation of transcription factor condensates involved in gene repression by ERK signaling in gastrulating embryos of a simple proto-vertebrate (Ciona). ERK signaling induces nuclear export of the transcriptional repressor ERF, which has been linked to various human developmental disorders. Using high resolution imaging we show that ERF is localized within discrete nuclear condensates that dissolve upon ERK activation. Interestingly, we observe dynamic pulses of assembly and dissociation during the cell cycle, providing the first visualization of a nuclear phase separation process that is regulated by cell signaling. We discuss the implications of these observations for producing sharp on/off switches in gene activity and suppressing noise in cell-cell signaling events.
Proteomics of colorectal cancer liver metastasis: A quantitative focus on drug elimination and pharmacodynamics effects
Authors: Vasilogianni Areti‐Maria , Al‐Majdoub Zubida M. , Achour Brahim , Peters Sheila Annie , Rostami‐Hodjegan Amin , Barber Jill 
Published: October 2021

AimsThis study aims to quantify drug‐metabolising enzymes, transporters, receptor tyrosine kinases (RTKs) and protein markers (involved in pathways affected in cancer) in pooled healthy, histologically normal and matched cancerous liver microsomes from colorectal cancer liver metastasis (CRLM) patients.MethodsMicrosomal fractionation was performed and pooled microsomes were prepared. Global and accurate mass and retention time liquid chromatography–mass spectrometry proteomics were used to quantify proteins. A QconCAT (KinCAT) for the quantification of RTKs was designed and applied for the first time. Physiologically based pharmacokinetic (PBPK) simulations were performed to assess the contribution of altered abundance of drug‐metabolising enzymes and transporters to changes in pharmacokinetics.ResultsMost CYPs and UGTs were downregulated in histologically normal relative to healthy samples, and were further reduced in cancer samples (up to 54‐fold). The transporters, MRP2/3, OAT2/7 and OATP2B1/1B3/1B1 were downregulated in CRLM. Application of abundance data in PBPK models for substrates with different attributes indicated substantially lower (up to 13‐fold) drug clearance when using cancer‐specific instead of default parameters in cancer population. Liver function markers were downregulated, while inflammation proteins were upregulated (by up to 76‐fold) in cancer samples. Various pharmacodynamics markers (e.g. RTKs) were altered in CRLM. Using global proteomics, we examined proteins in pathways relevant to cancer (such as metastasis and desmoplasia), including caveolins and collagen chains, and confirmed general over‐expression of such pathways.ConclusionThis study highlights impaired drug metabolism, perturbed drug transport and altered abundance of cancer markers in CRLM, demonstrating the importance of population‐specific abundance data in PBPK models for cancer.
Association of prior local therapy and outcomes with programmed‐death ligand‐1 inhibitors in advanced urothelial cancer
Authors: Makrakis Dimitrios , Talukder Rafee , Diamantopoulos Leonidas N. , Carril‐Ajuria Lucia , Castellano Daniel , De Kouchkovsky Ivan , Koshkin Vadim S. , Park Joseph J. , Alva Ajjai , Bilen Mehmet A. , Stewart Tyler F. , McKay Rana R. , Santos Victor S. , Agarwal Neeraj , Jain Jayanshu , Zakharia Yousef , Morales‐Barrera Rafael , Devitt Michael E. , Grant Michael , Lythgoe Mark P. , Pinato David J. , Nelson Ariel , Hoimes Christopher J. , Shreck Evan , Gartrell Benjamin A. , Sankin Alex , Tripathi Abhishek , Zakopoulou Roubini , Bamias Aristotelis , Murgic Jure , Fröbe Ana , Rodriguez‐Vida Alejo , Drakaki Alexandra , Liu Sandy , Kumar Vivek , Di Lorenzo Giuseppe , Joshi Monika , Isaacsson‐Velho Pedro , Buznego Lucia Alonso , Duran Ignacio , Moses Marcus , Barata Pedro , Sonpavde Guru , Yu Evan Y. , Wright Jonathan L. , Grivas Petros , Khaki Ali Raza 
Published: October 2021

ObjectivesTo compare clinical outcomes with programmed‐death ligand‐1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease.Patients and MethodsWe performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression‐free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first‐line and second‐line or greater [second‐plus line]). Logistic regression was used to compare ORR, while Kaplan–Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors.ResultsWe included 562 patients (first‐line: 342 and second‐plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first‐line ICIs. In the second‐plus‐line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19–5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42–0.88) and PFS (aHR 0.63, 95% CI 0.45–0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately.ConclusionPrior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second‐plus‐line but not in the first‐line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study’s retrospective nature, lack of randomization, and possible selection and confounding biases.
Serum testosterone and oestradiol predict the growth response during puberty promoting treatment
Authors: Huttunen Heta , Varimo Tero , Huopio Hanna , Voutilainen Raimo , Tenhola Sirpa , Miettinen Päivi J. , Raivio Taneli , Hero Matti 
Published: October 2021

AbstractObjectiveThe influence of androgens and oestrogens on growth is complex, and understanding their relative roles is important for optimising the treatment of children with various disorders of growth and puberty.DesignWe examined the proportional roles of androgens and oestrogens in the regulation of pubertal growth in boys with constitutional delay of growth and puberty (CDGP). The study compared 6‐month low‐dose intramuscular testosterone treatment (1 mg/kg/month; n = 14) with per oral letrozole treatment (2.5 mg/day; n = 14) which inhibits conversion of androgens to oestrogen.PatientsBoys with CDGP were recruited to a randomized, controlled, open‐label trial between 2013 and 2017 (NCT01797718).MeasurementsThe patients were evaluated at 0‐, 3‐ and 6‐month visits, and morning blood samples were drawn. Linear regression models were used for data analyses.ResultsIn the testosterone group (T‐group), serum testosterone concentration correlated with serum oestradiol concentration at the beginning of the study and at 3 months, whereas in the letrozole group (Lz‐group) these sex steroids correlated only at baseline. Association between serum testosterone level and growth velocity differed between the T and Lz groups, as each nmol/L increase in serum testosterone increased growth velocity 2.7 times more in the former group. Serum testosterone was the best predictor of growth velocity in both treatment groups. In the Lz‐group, adding serum oestradiol to the model significantly improved the growth estimate. Only the boys with serum oestradiol above 10 pmol/L had a growth velocity above 8 cm/year.ConclusionsDuring puberty promoting treatment with testosterone or aromatase inhibitor letrozole, growth response is tightly correlated with serum testosterone level. A threshold level of oestrogen appears to be needed for an optimal growth rate that corresponds to normal male peak height velocity of puberty. Serum testosterone 1 week after the injection and serum testosterone and oestradiol 3 months after the onset of aromatase inhibitor treatment can be used as biomarkers for treatment response in terms of growth.
The association between joint physical custody and children’s mental health. Do children’s experiences of parental loyalty conflicts moderate the relationship?
Authors: Augustijn Lara 
Published: October 2021

AbstractThis study investigated the association between joint physical custody (JPC), parental loyalty conflict (PLC) behaviours and children's mental health in a sample of 284 children aged 11 to 14 from the FAMOD survey. The results of the linear regression models indicated that children in JPC families had better mental health than children in sole physical custody families, and that PLC behaviours negatively affected children's mental health. Furthermore, children's experiences of PLC behaviours moderated the association between JPC and their mental health, with high levels of PLC behaviours leading to a noticeable decline in the mental health of children in JPC families.
Single‐nucleotide polymorphism in chronic rhinosinusitis: A systematic review
Authors: Antonino Maniaci , Nicolò Musso , Jerome Renee Lechien , Federico Merlino , Chiara Viglianisi , Stefano Stracquadanio , Maria Santagati , Salvatore Cocuzza , Antonio Bonanno , Calvo‐Henriquez Christian , Stefania Stefani , La Mantia Ignazio 
Published: October 2021

AbstractObjectivesWe performed a systematic review on single‐nucleotide polymorphisms and risk‐related chronic rhinosinusitis.Design and SettingA comprehensive review of the last 20 years’ English language literature regarding chronic rhinosinusitis and single‐nucleotide polymorphisms was performed. We included in the synthesis all the papers reporting gene variation implicated in the pathogenesis of chronic inflammation and polyps.ResultsWe found 12 papers with 9127 patients, of which 2739 CRS cases and 6388 controls. The major comorbidities reported related to chronic rhinosinusitis were atopy in 4555 (49.9%), asthma in 4594 (50.33%), Samter Triad in 448 (4.9%) and eosinophilia in 391 subjects (4.28%).ConclusionOur systematic review revealed the major SNPs significantly associated with chronic rhinosinusitis and the specific pathways involved. Given the presence of different extraction methods and samples sequencing, further studies with larger courts are necessary to identify significative single‐nucleotide polymorphisms.