bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating the role of Cavin1 in drug-induced long QT syndrome (diLQTS)
Authors: Al Sayed Z R , Pereira C , Jouve C , Hulot J.-S 
Published: October 2021

Abstract

Introduction
Several drugs can induce QT prolongation by altering cardiac ion currents, notably IKr. The cardiotoxic response to a drug is however extremely variable between individuals, ranging from no impact to life-threatening ventricular arrhythmias. The molecular mechanisms underlying this variability remain unclear. Previously, we reported higher expression levels of Cavin1, an essential protein for caveolae formation, in cardiomyocytes (CM) derived from patients with high susceptibility to develop sotalol-induced long QT.

Purpose
We aimed to explore whether Cavin1 could sway the cardiac repolarization response to drugs.

Method
We used induced pluripotent stem cells-derived CM (iPS-CM) from two subjects with the highest sensitivity (HS) to sotalol (ie, those with the highest increase in QTc) and two individuals with the lowest sensitivity to sotalol (LS) to perform molecular and electrophysiological investigations.

Results
At baseline, no differences in terms of repolarization durations, IKr amplitude, and ion channel expression were noted between the HS- and the LS-iPS-CM. However, the HS-iPS-CM displayed significant prolongation in action potential and field potential (FPD) durations after the application of 30 and 50μM of sotalol. They also displayed higher sensitivity to other drugs targeting hERG (E4031, vandetanib, and clarithromycin). Cavin1 mRNA and protein levels were increased by 2 fold in the HS-iPS-CM as compared to the LS-iPS-CM. Overexpressing Cavin1 in the LS-iPS-CM using adenovirus induced a higher sensitivity to sotalol as only 10μM was sufficient to induce 12% longer FPD. Consistently, the infection with Cavin1 increased the sensitivity of LS-CM to the other hERG blockers. In contrast, siRNA against Cavin1 reduced its expression by 60% in HS iPS-CM and switched their phenotype to a lower sensitivity to sotalol and the other hERG blockers. Interestingly, in line with the shortening of the FPD in LS-iPS-CM, overexpressing Cavin1 increased hERG expression in isolated membrane fraction from HEK cells stably expressing KCNH2. This suggests a role of Cavin1 in modulating hERG trafficking/recycling to the membrane and thereby the number of channels that can be blocked by drugs.

Conclusion
Altogether, this work identified Cavin1 as a novel modulator of cardiomyocyte response to hERG blockers and a potential risk factor for diLQT. Further understanding of its contribution may pave the way for personalized drug prescription to avoid undesirable cardiotoxicity.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Leducq
Implantable cardioverter-defibrillators and the older patient: the Dutch clinical practice
Authors: Yilmaz Dilek , Egorova Anastasia D , Schalij Martin J , van Erven Lieselot 
Published: October 2021

Abstract

Background and objective
Balance between benefit and burden of implantable cardioverter-defibrillator (ICD) therapy is more debatable in older patients, compared to younger patients. Of around 6000 yearly implanted ICDs in the Netherlands, 1:4 is received by patients ≥75 years. We aimed to evaluate the current clinical practice in the Netherlands for ICD implants and generator replacements, with a special focus on the older ICD patients.

Research design and methods
Cardiologists from all Dutch ICD implanting centres (n = 28) were interviewed. Questions aimed to evaluate outpatient care, pre-operative patient assessment, end-of-life-care counselling, evaluation of social and cognitive wellbeing, clinical evaluation of all patients prior to ICD replacement, and the consideration of the option to downgrade or not replace a device.

Results
Implanting cardiologists from all 28 implanting centres were approached for an interview. Response rate was 86%. Management appeared diverse. An age ≥80 years was consistently reported as incentive for more extensive patient evaluation. Patients were invited for counselling prior to device replacements in only the minority (46%) of hospitals. Downgrade or non-replacement was performed in rare cases. End-of-life care discussions were not standard procedure in 67% of the hospitals. Evaluation of social and cognitive wellbeing of patients was based solely on the general clinical impression of the physician in 83%, or not at all assessed in 8% of the centres.

Discussion and implication
A structured framework for care and evaluation of cognitive and/or physical limitations is currently absent in most hospitals. At time of ICD (re-)evaluation, several factors may be considered before deciding on (continuation of) ICD therapy: patient preferences and comorbidity, the need for pacemaker therapy, primary vs. secondary prevention, procedural risks, and patient preferences.
Genic Selection Within Prokaryotic Pangenomes
Authors: Douglas Gavin M , Shapiro B Jesse 
Published: October 2021

Abstract
Understanding the evolutionary forces shaping prokaryotic pangenome structure is a major goal of microbial evolution research. Recent work has highlighted that a substantial proportion of accessory genes appear to confer niche-specific adaptations. This work has primarily focused on selection acting at the level of individual cells. Herein, we discuss a lower level of selection that also contributes to pangenome variation: genic selection. This refers to cases where genetic elements, rather than individual cells, are the entities under selection. The clearest examples of this form of selection are selfish mobile genetic elements, which are those that have either a neutral or a deleterious effect on host fitness. We review the major classes of these and other mobile elements and discuss the characteristic features of such elements that could be under genic selection. We also discuss how genetic elements that are beneficial to hosts can also be under genic selection, a scenario that may be more prevalent but not widely appreciated, because disentangling the effects of selection at different levels (i.e., organisms vs. genes) is challenging. Nonetheless, an appreciation for the potential action and implications of genic selection is important to better understand the evolution of prokaryotic pangenomes.
Controls on surface wave overtone interference
Authors: Hariharan Anant , Dalton Colleen A , Babikoff Jordyn , Ekström Göran 
Published: October 2021

SUMMARYMeasurements of fundamental-mode (FM) surface waves along the minor arc are impacted by overtone interference. This interference is primarily due to major-arc overtones for Rayleigh waves and minor-arc overtones for Love waves. In both cases, interference contaminates measurements of phase and amplitude and can introduce bias in seismic images. Here, we use synthetic seismograms computed via normal mode summation to probe how interference can vary as a function of the surface wave group velocities, source mechanism and depth, which control the relative excitation of the FM and overtones, and period. By comparing seismograms that include all overtones to those that include only the FM, we can quantify the interference, i.e., how the presence of the overtones perturbs the FM phase and amplitude. We compare the strength of this interference to calculations of excitation of the overtones and FM. We show that these calculations explain well the varying strength of interference for different source mechanisms and depths. Notably, these calculations illuminate source depths where Love wave overtone excitation is quite low and therefore interference is unusually weak, and depths where Rayleigh wave FM excitation is low and therefore interference is unusually strong. Our analysis also reinforces the dependence of the interference on the FM and overtone group velocities. For Love waves, this results in weak minor-arc overtone interference at long periods and, for continental paths, short periods. For Rayleigh waves, the differing overtone and FM group velocities and the relative excitation of the overtones and FM explain rapid variations in the strength of Rayleigh wave major-arc overtone interference as a function of epicentral distance. We then show that real data are affected by the relative excitation of the FM and overtones. We find that errors in Rayleigh wave phase velocities determined at the EarthScope USArray stations are larger when the ratios of overtone to FM excitation are larger. We also find a dependence of phase velocity error on excitation ratio for Love waves, and we identify the presence of major-arc overtone interference in Love wave measurements. Our results highlight opportunities for more nuanced quality control of surface wave measurements. The relative excitation ratio of the overtones and FM may be a better criterion for event selection than source depth, allowing deeper events that well excite FMs to be included and shallower events with large overtone excitation to be excluded. This would allow the collection of more accurate measurements that will increase the precision of seismic images.
Slow slip events precursory to the 2014 Iquique Earthquake, revisited with long-base tilt and GPS records
Authors: Boudin F , Bernard P , Meneses G , Vigny Ch , Olcay M , Tassara C , Boy J P , Aissaoui E , Métois M , Satriano C , Esnoult M-F , Nercessian A , Vallée M , Vilotte J-P , Brunet Ch 
Published: October 2021

SUMMARY
The M= 8.1, 1 April 2014 Iquique earthquake, which broke part of the northern Chile seismic gap, was preceded by a strong foreshock sequence starting early January 2014. The reported analysis of the continuous records of the nearby GPS stations from the Integrated Plate Observatory Chile, North Chile array lead to contradictory results concerning the existence and location of slow slip events (SSEs) on the interplate contact. Resolving this controversy is an important issue, as although many SSEs are reported in subduction zones, only a few were found to be precursory to large earthquakes. Here we show that the records of a long base tiltmeter installed near Iquique, when corrected for coseismic steps, long-term drift, tidal signals and oceanic and atmospheric loading, show significant residual signals. These can be modelled with a sequence of four SSEs located close to Iquique. Their signature was already reported on some GPS stations, but their source was then characterized with a very low resolution in time and space, leading to contradicting models. With the tilt records, we can rule out the previously proposed models with a single large SSE closer to the main shock. Combining tilt with GPS records greatly improves the resolution of GPS alone, and one could locate their sources 100–180 km south–southeast to the main shock epicentre, with moment magnitudes between 5.8 and 6.2, at the edge of the main aftershock asperities. These moderate SSEs thus did not directly trigger the main shock, but contributed to trigger the main foreshock and the main aftershock. Only the sensitivity and resolution of the tiltmeter, added to the GPS records, allowed us to describe with unprecedented accuracy this precursory process as a cascade of cross-triggered, short-term aseismic slip events and earthquakes on the interplate contact. This three months of precursory activation appears to be the final acceleration burst of a weaker, longer term SSE which started mid-2013, already reported, with a moment release history which we could quantify. From the methodological point of view, our study takes advantage of an interesting complementarity of tilt and GPS measurements, due to their different dependence in distance to the source of strain, which turns out to be very efficient for resolving location and moment of strain sources, even when both instruments are close to each other. It finally demonstrates the efficient removal of sequences of small or even undetected coseismic steps from high resolution tilt record signal in order to retrieve the purely aseismic signal, a presently impossible task for high time resolution GPS records due to low signal to noise.
C/D box snoRNA SNORD113-6/AF357425 plays a dual role in integrin signalling and arterial fibroblast function via pre-mRNA processing and 2′O-ribose methylation
Authors: van Ingen Eva , van den Homberg Daphne A L , van der Bent M Leontien , Mei Hailiang , Papac-Milicevic Nikolina , Kremer Veerle , Boon Reinier A , Quax Paul H A , Wojta Johann , Nossent A Yaël 
Published: October 2021

Abstract
We have previously shown that C/D box small nucleolar RNAs (snoRNAs) transcribed from the DLK1-DIO3 locus on human chromosome 14 (14q32) are associated with cardiovascular disease. DLK1-DIO3 snoRNAs are ‘orphan snoRNAs’ that have no known targets. We aimed to identify RNA targets and elucidate the mechanism-of-action of human SNORD113-6 (AF357425 in mice). As AF357425-knockout cells were non-viable, we induced overexpression or inhibition of AF357425 in primary murine fibroblasts and performed RNA-Seq. We identified several pre-mRNAs with conserved AF357425/SNORD113-6 D′-seed binding sites in the last exon/3′ untranslated region (3′UTR), which directed pre-mRNA processing and splice-variant-specific protein expression. We also pulled down the snoRNA-associated methyltransferase fibrillarin from AF357425-High versus AF357425-Low fibroblast lysates, followed by RNA isolation, ribosomal RNA depletion and RNA-Seq. Identifying mostly mRNAs, we subjected these to PANTHER pathway analysis and observed enrichment for genes in the integrin pathway. We confirmed 2′O-ribose methylation in six integrin pathway mRNAs (MAP2K1, ITGB3, ITGA7, PARVB, NTN4 and FLNB). Methylation and mRNA expressions were decreased while mRNA degradation was increased under AF357425/SNORD113-6 inhibition in both murine and human primary fibroblasts, but effects on protein expression were more ambiguous. Integrin signalling is crucial for cell–cell and cell–matrix interactions, and correspondingly, we observed altered human primary arterial fibroblast function upon SNORD113-6 inhibition.
Quantifying bycatch risk factors for the Chinese distant water fishery
Authors: Xia Meng , Carruthers Tom , Kindong Richard , Dai Libin , Geng Zhe , Dai Xiaojie , Wu Feng 
Published: October 2021

AbstractMitigating bycatch of non-target fish species is a common objective in fisheries management that may be supported by the gathering of data from fishery observer programs and quantitative analysis of bycatch risk factors. We build three GLM models based on Chinese tuna longline fishery observer data in terms of analysis of total bycatch rate (TB rate), total bycatch ratio (TB ratio), and species-specific bycatch rate, respectively. The positive log-linear models assumed a Gaussian observation error model and a linear combination of categorical independent variables, including area, year, month, depth, and bycatch species. Results show that distributions of TB rate and TB ratio followed different trends and a latitudinal decrease was observed from both the northern and southern hemisphere of the equator. Comprehensively, the Pacific is a better place to fish compared to the Indian and Atlantic Oceans in terms of relatively lower TB rate and TB ratio. Fishing in open oceans can somehow avoid a high TB ratio than fishing in coastal waters. As a result, we recommend area 2SW, 2SE, 2 NW, 14SW, 14SE, and 14 NW as appropriate fishing ground for Albacore (Thunnus alalunga) while area 11N, 11S, 18SW, and 18SE to be appropriate fishing ground for fishing bigeye tuna (Thunnus obesus). Setting fishing gears deeper than 500 m would also help to get a low TB rate and TB ratio.
How does structure matter? Comparison of canopy photosynthesis using one- and three-dimensional light models: a case study using greenhouse cucumber canopies
Authors: Pao Yi-Chen , Kahlen Katrin , Chen Tsu-Wei , Wiechers Dirk , Stützel Hartmut 
Published: October 2021

Abstract
One-dimensional light models using the Beer–Lambert equation (BL) with the light extinction coefficient k are simple and robust tools for estimating light interception of homogeneous canopies. Functional–structural plant models (FSPMs) are powerful to capture light–plant interactions in heterogeneous canopies, but they are also more complex due to explicit descriptions of three-dimensional plant architecture and light models. For choosing an appropriate modelling approach, the trade-offs between simplicity and accuracy need to be considered when canopies with spatial heterogeneity are concerned. We compared two light modelling approaches, one following BL and another using ray tracing (RT), based on a framework of a dynamic FSPM of greenhouse cucumber. Resolutions of hourly step (HS) and daily step (DS) were applied to simulate light interception, leaf-level photosynthetic acclimation and plant-level dry matter production over growth periods of 2–5 weeks. Results showed that BL-HS was comparable to RT-HS in predicting shoot dry matter and photosynthetic parameters. The k used in the BL approach was simulated using an empirical relationship between k and leaf area index established with the assistance of RT, which showed variation up to 0.2 in k depending on canopy geometry under the same plant density. When a constant k value was used instead, a difference of 0.2 in k resulted in up to 27 % loss in accuracy for shoot dry matter. These results suggested that, with the assistance of RT in k estimation, the simple approach BL-HS provided efficient estimation for long-term processes.
Association between place of delivery, assistance during delivery and fistula occurrence in Afghanistan
Authors: Samad Nandeeta , Das Pranta , Ahinkorah Bright Opoku , Seidu Abdul-Aziz , Mohammed Aliu , Frimpong James Boadu , Mitra Dipak Kumar 
Published: October 2021

Abstract

Background
Obstetric fistula is one of themost serious and devastating childbirth-related injuries women suffer worldwide. This study investigated the association between delivery characteristics and the occurrence of obstetric fistula in Afghanistan.

Methods
The study analysed data from the 2015 Afghanistan Demographic and Health Survey. The association between place of delivery and assistance during delivery with experience of fistula symptoms was investigated by fitting two binary logistic regression models.

Results
Findings from this study revealed that 23.4% of the women surveyed ever heard about obstetric fistula and 3% reported symptoms of fistula. Women whose deliveries were assisted by traditional birth attendants were significantly more likely to experience fistula compared with those whose deliveries were assisted by doctors. Similarly, women whose deliveries were assisted by others were significantly more likely to experience fistula compared with women whose deliveries were assisted by doctors. Regarding place of delivery, women whose deliveries took place at a government hospital were less likely to experience fistula compared with those whose deliveries took place at home.

Conclusions
This study highlights the importance of skilled delivery in reducing the risk for obstetric fistula among women in Afghanistan. Therefore, it is important for the various stakeholders in Afghanistan's healthcare delivery system, including healthcare providers, local authorities and international non-governmental organisations, to collaborate and institute measures that will promote health facility deliveries and improve access to skilled delivery.
PSII-12 Identifying behaviors and the ‘normal’ daily ethogram using accelerometers on grazing animals
Authors: Catrett Cassidy C , Parsons Ira L , Dentinger Jane E , Norman Durham A , Webb Stephen L , Stone Amanda E , Street Garrett , Karisch Brandi B 
Published: October 2021

Abstract
Animal behavior plays a crucial role as an indicator of animal health and nutritional status and serves as an indicator of animal growth. The objective of this study was to build an ethogram describing behavior in grazing cattle. We collected video and accelerometer data from crossbred steers (n = 10) used as part of a larger grazing study on the HH Leveck Animal Research Center, Mississippi State, MS. Daily Diary accelerometers (Wildbyte® technologies, Swansea) were programmed to collect magnetometer and accelerometer data at 40 Hz and attached to the GPS collars fitted on the animals prior to their release into a 10-hectare pasture of Tall Fescue and Bermudagrass, overseeded with Annual Ryegrass. Automated camera traps (Bushnell Essential®) were synced with UTC time and programmed to record 30-second video clips when triggered. Approximately 387,000 accelerometer signals representing 161 minutes of behavior from 10 animals were recorded, and behavior classified according to 1 of 5 categories: traveling, foraging, resting, ruminating, and grooming (Kilgour et al., 2012). Categorized accelerometer data was used to train a random forest model (Liaw and Weiner, 2002) in Program R (R Core Team, 2020), which resulted in a model sensitivity of 0.97, 0.93, 0.90, 0.87, and 0.80 for Traveling, Foraging, Resting, Ruminating, and Grooming, respectively, and an overall model accuracy of 0.95. Behaviors were aggregated into behavior bouts, and a daily ethogram was calculated for March 2019. This revealed that the steers spent the most amount of time traveling, an average of 1,026 minutes per day. This behavior was followed, in the average length of time, by foraging and resting for 205 ± 52.8 minutes and 31.8 ± 28.2 minutes per day, respectively. These results indicate the ability to accurately build a behavioral ethogram for grazing cattle and warrant further study in future research and livestock management.
PSXV-22 Effect of inclusion of dried citrus pulp in the receiving supplement for newly received stocker cattle
Authors: Yeatter Haley , Kegley Beth B , Cauble Reagan N , Reynolds Jana , Shoulders Ben P , Powell Jeremy G 
Published: October 2021

Abstract
Citrus pulp is a source of flavonoids which have been found to have antioxidant properties. Thus, the objective of this experiment was to investigate the effects of feeding dried citrus pulp on performance of newly received calves. Crossbred beef heifers (n = 254, initial body weight = 248 ± 5.9 kg) were obtained on 3 dates (block, 8 pens/block). Treatments were: 1) a corn and distillers’ grains based receiving supplement (control) or 2) a receiving supplement that contained 20% dried citrus pulp (replacing a portion of the corn). Upon arrival from regional livestock markets, cattle had access to hay and water and rested overnight then were processed the next day in which they received an identification tag, were vaccinated with a clostridial and a 5-way modified live bovine respiratory viral, dewormed, weighed, branded, and ear notched for detection of persistent infection with bovine viral diarrhea virus. Each truckload was assigned randomly to pens resulting in 8 pens with 9 to 12 heifers/pen. Pens were assigned randomly to 1 of the 2 treatments. Cattle were offered bermudagrass hay and water for ad libitum intake and were offered up to 1.8 kg/day of their appropriate receiving supplement. Overall average daily gain for the 42-day receiving period was increased (P &lt; 0.01) for calves fed the supplement that included dried citrus pulp (1.01 kg/day) compared to the calves fed the control supplement (0.90 kg/day). However, the percentage of calves treated for clinical bovine respiratory disease was increased (P &lt; 0.05) for calves fed the citrus pulp containing supplement (14% morbidity) compared to control calves (7% morbidity). The supplementation of dried citrus pulp to calves improved growth performance, but did not reduce the incidence of clinical bovine respiratory disease during the receiving period; however, clinical morbidity was low for both treatments.