bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel workflow to improve genotyping of multigene families in wildlife species: An experimental set‐up with a known model system
Authors: Gillingham Mark A. F. , Montero B. Karina , Wihelm Kerstin , Grudzus Kara , Sommer Simone , Santos Pablo S. C. 
Published: October 2020

AbstractGenotyping complex multigene families in novel systems is particularly challenging. Target primers frequently amplify simultaneously multiple loci leading to high PCR and sequencing artefacts such as chimeras and allele amplification bias. Most genotyping pipelines have been validated in nonmodel systems whereby the real genotype is unknown and the generation of artefacts may be highly repeatable. Further hindering accurate genotyping, the relationship between artefacts and genotype complexity (i.e. number of alleles per genotype) within a PCR remains poorly described. Here, we investigated the latter by experimentally combining multiple known major histocompatibility complex (MHC) haplotypes of a model organism (chicken, Gallus gallus, 43 artificial genotypes with 2–13 alleles per amplicon). In addition to well‐defined ‘optimal’ primers, we simulated a nonmodel species situation by designing ‘cross‐species’ primers based on sequence data from closely related Galliform species. We applied a novel open‐source genotyping pipeline (ACACIA; https://gitlab.com/psc_santos/ACACIA), and compared its performance with another, previously published pipeline (AmpliSAS). Allele calling accuracy was higher when using ACACIA (98.5% versus 97% and 77.8% versus 75% for the ‘optimal’ and ‘cross‐species’ data sets, respectively). Systematic allele dropout of three alleles owing to primer mismatch in the ‘cross‐species’ data set explained high allele calling repeatability (100% when using ACACIA) despite low accuracy, demonstrating that repeatability can be misleading when evaluating genotyping workflows. Genotype complexity was positively associated with nonchimeric artefacts, chimeric artefacts (nonlinearly by levelling when amplifying more than 4–6 alleles) and allele amplification bias. Our study exemplifies and demonstrates pitfalls researchers should avoid to reliably genotype complex multigene families.
Cognitive control beliefs and cognitive functioning in mid‐ to late‐life
Authors: Raldiris Tarah L. , Perez Elliottnell , Donovan Emily K. , Dzierzewski Joseph M. 
Published: October 2020

ObjectivesOlder adults experience age‐related cognitive declines and often feel as if the severity of these declines is out of their control. Recent research suggests, though, that control beliefs may be related to less age‐related declines. The aim of the current study was to investigate cognitive domain‐specific control beliefs and the link between those cognitive control beliefs and cognitive functioning among a nationwide sample of adults (N = 3,670), as well as to explore whether cognitive control beliefs moderated the relationship between age and cognitive functioning.MethodThe aims were addressed using data from the national Midlife in the United States study (MIDUS II). Cognitive functioning was assessed using the Brief Test of Adult Cognition by Telephone (BTACT), and cognitive control beliefs were assessed with the Personality in Intellectual Aging Contexts (PIC) Inventory Control Scales.ResultsRegression analyses revealed that adults with higher control beliefs demonstrated better cognitive functioning. Moderation analyses indicated cognitive control beliefs moderated the relationship between age and executive functioning, but not the association between age and episodic memory.ConclusionResults suggested that the relationship between age and executive functioning was weaker at high levels of cognitive control beliefs. Future research should establish the directionality of the effect between cognitive control beliefs and cognition and investigate the association between control beliefs and cognition in samples at higher risk for substantial cognitive decline, including the oldest‐old.
Endobronchial ultrasound guided transbronchial cryobiopsy versus forceps biopsy in peripheral lung lesions
Authors: Torky Mohamed , Elshimy Wafaa S. , Ragab Mohamed AE. , Attia Ghada A. , Lopez Raquel , Mate Jose Luis , Centeno Carmen , Serra Pere , Tazi Mezalek Rachid , Pérez Eli Nancy , Manzano Juan Ruiz , Rosell Antonio , Andreo Felipe 
Published: October 2020

AbstractIntroductionRadial probe endobronchial ultrasound (RP‐EBUS) is a modern technique for diagnosis of peripheral lung lesions. It is assumed that the addition of transbronchial cryobiopsy (TBCB) could increase the diagnostic value for RP‐EBUS.ObjectivesThe main objectives were to evaluate the efficacy and safety of RP‐EBUS‐guided TBCB for diagnosis of peripheral lung lesions and comparing it with RP‐EBUS‐guided transbronchial forceps biopsy.MethodsSixty patients with peripheral lung diseases were divided into two groups. Group I included 45 patients who were eligible for TBCB and they subjected to forceps transbronchial biopsy (forceps TBB) and TBCB guided by RP‐EBUS. Fifteen patients who were not eligible for TBCB were included in group II and they were subjected to forceps TBB and/or cytology retrieval procedures guided by RP‐EBUS.ResultsIn group I, forceps TBB had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of; 67.5%, 100%, 100%, 18.8%, and 69.8%, respectively, while TBCB had sensitivity, specificity, PPV, NPV, and accuracy of 75%, 100%, 100%, 23.1%, and 76.7%, respectively. The sensitivity in group II was 80% and the overall results including both groups were sensitivity, specificity, PPV, NPV, and accuracy of 85.2%, 100%, 100%, 42.8%, and 86.7%, respectively. Regarding the complications, only one patient (1.7%) had significant bleeding. One patient (1.7%) had pneumothorax and another patient (1.7%) suffered from hypoxemia.ConclusionsRP‐EBUS‐guided TBCB is a safe and effective technique for diagnosis of peripheral lung lesions. TBCB has achieved higher diagnostic values and better quality of samples.
Visual function subtyping in children with early‐onset cerebral visual impairment
Authors: Sakki Hanna , Bowman Richard , Sargent Jenefer , Kukadia Roopen , Dale Naomi 
Published: October 2020

AimTo develop a data‐driven subgrouping method to identify and profile subtypes of early‐onset childhood cerebral visual impairment (CVI).MethodSixty‐three children with suspected or diagnosed congenital CVI were recruited (28 males, 35 females, median age=8y, range=5–16y). Cognitive, basic, and higher‐order vision functions were assessed and quality of life, functional vision questionnaire, neurodevelopmental, and ophthalmological data were collected. Cluster analysis and other statistical analyses were undertaken to determine and validate the subgrouping.ResultsForty‐three participants completing the full test battery were included in cluster analysis, revealing two subgroups. Group A1 (n=15) showed selective visual perception and visuomotor deficits. Group A2 (n=28) showed more severe and broader visual perception and visuomotor deficits, and variable visual acuity. A third, lower‐functioning group, Group B (n=20), was differentiated and showed significant visual acuity reduction compared with Group A (p<0.001, V=0.69). External validation showed significant cooccurring ophthalmological (e.g. strabismus p<0.001, V=0.59) and motor impairment differences (χ2=16.26, p<0.001, V=0.51) between the three groups. All groups had lowered parent‐reported quality of life and everyday functional vision.InterpretationStatistical analyses revealed three subgroups with differentiated vision function characteristics on a gradient of severity. The subgrouping method provides the first steps in developing a novel classification system to underpin future clinical diagnostics and profiling of early‐onset CVI.What this paper adds

Three data‐driven subgroups of vision function deficits were identified.

A similar severity gradient was shown in cooccurring cognitive and neurodevelopmental deficits.

Reported quality of life and functional vision difficulties were low across all groups.
How low can we go? Influence of sample rate on equine pelvic displacement calculated from inertial sensor data
Authors: Pfau Thilo , Reilly Patrick 
Published: October 2020

AbstractBackgroundLow‐cost sensor devices are often limited in terms of sample rate. Based on signal periodicity, the Nyquist theorem allows determining the minimum theoretical sample rate required to adequately capture cyclical events, such as pelvic movement in trotting horses.ObjectivesTo quantify the magnitude of errors arising with reduced sample rates when capturing biological signals using the example of pelvic time‐displacement series and derived minima and maxima used to quantify movement asymmetry in lame horses.Study designData comparison.MethodsRoot mean square (RMS) errors between the ‘reference’ time‐displacement series, captured with a validated inertial sensor at 100 Hz sample rate, and down‐sampled time‐series (8 Hz to 50 Hz) are calculated. Accuracy and precision are determined for maxima and minima derived from the time‐displacement series.ResultsAverage RMS errors are <2 mm at 50 Hz sample rate, <4 mm at 40 Hz, <7 mm between 25 and 35 Hz, and increase to up to 20 mm at 20 Hz and below. Accuracy for maxima and minima is generally below 1mm. Precision is 1 mm at 50 Hz sample rate, 3 mm at 40Hz and ≥9 mm at 20 Hz and below.Main limitationsOnly sample rate, no other sensor parameters were investigated.ConclusionsSample rate related errors for inertial sensor derived time‐displacement series of pelvic movement are <2mm at 50 Hz, a rate that many low‐cost loggers, smartphones or wireless sensors can sustain hence rendering these devices valid options for quantifying parameters relevant for lameness examinations in horses.
Implantable loop recorders can detect paroxysmal atrial fibrillation in Standardbred racehorses with intermittent poor performance
Authors: Buhl Rikke , Nissen Sarah D. , Winther Marie L. K. , Poulsen Sofie K. , Hopster‐Iversen Charlotte , Jespersen Thomas , Sanders Prashanthan , Carstensen Helena , Hesselkilde Eva M. 
Published: October 2020

AbstractBackgroundLimited information is available on paroxysmal atrial fibrillation (PAF) in the horse. Indeed, undiagnosed PAF could result in poor performance. Due to the intermittent occurrence, PAF is difficult to diagnose. However, implanting a small ECG device (implantable loop recorder, ILR) subcutaneously, allows the continuous and automatic detection of PAF.ObjectivesThe aim was to investigate the potential of ILRs as a tool for diagnosing PAF in horses with poor performance.Study designProspective field study.MethodsTwelve racing Standardbred trotters with intermittent reduced performance (mean age: six years) were enrolled prospectively. The ILR was implanted subcutaneously at the fifth or sixth left intercostal space and data from the ILR was collected during the study period in which the horses were followed for a median duration of 7.5 month (range 6‐28).ResultsThe ILR was able to detect PAF in four out of twelve racehorses. The ILR also detected sustained atrial fibrillation (AF) in one horse during the study. The ILRs rely on RR detection and R waves were correctly identified in 96%. One hundred episodes were categorised as AF by the ILRs and subsequently visual ECG inspection categorised 12 as sinus rhythm (SR), 28 as sinus arrhythmia (SA), 14 as other arrhythmias and 46 as AF episodes. The Root Mean Square of the Successive Differences (RMSSD) values were significantly increased for AF compared to SR and SA.Main limitationsFew horses included and duration of study period varied among the horses. Further it was not possible to assess the sensitivity of the device in the current study and the ILRs proved to have a high rate of false positive misclassifications.ConclusionsThis study indicates that ILRs can be used for detection of PAF episodes and could be a useful ECG tool for horses presenting with poor performance. This methodology provides a platform to facilitate the long‐term assessment of AF development and quantification of AF burden in horses. Further studies including both healthy and poor performing horses are needed in order to learn more about PAF prevalence in racehorses.
Stimulation of GMP formation in hGBP1 is mediated by W79 and its effect on the antiviral activity
Authors: Raninga Nikunj , Nayeem Shahid M. , Gupta Sowmiya , Mullick Ranajoy , Pandita Esha , Das Saumitra , Deep Shashank , Sau Apurba Kumar 
Published: October 2020

Interferon‐inducible large GTPases are critical for innate immunity. The distinctive feature of a large GTPase, human guanylate binding protein‐1 (hGBP1), is the sequential hydrolysis of GTP into GMP via GDP. Despite several structural and biochemical studies, the underlying mechanism of assembly‐stimulated GMP formation by hGBP1 and its role in immunity are not fully clarified. Using a series of biochemical, biophysical, and in silico experiments, we studied four tryptophan residues, located near switch I‐II (in and around the active site) to understand the conformational changes near these regions and also to investigate their effect on enhanced GMP formation. The W79A mutation showed significantly reduced GMP formation, whereas the W81A and W180A substitutions exhibited only a marginal defect. The W114A mutation showed a long‐range effect of further enhanced GMP formation, which was mediated through W79. We also observed that after first phosphate cleavage, the W79‐containing region undergoes a conformational change, which is essential for stimulated GMP formation. We suggest that this conformational change helps to reposition the active site for the next cleavage step, which occurs through a stable contact between the indole moiety of W79 and the main chain carbonyl of K76. We also showed that stimulated GMP formation is crucial for antiviral activity against hepatitis C. Thus, the present study not only provides new insight for the stimulation of GMP formation in hGBP1, but also highlights the importance of the enhanced second phosphate cleavage product in the antiviral activity.
Linkage mapping evidence for a syntenic QTL associated with flowering time in perennial C4 rhizomatous grasses Miscanthus and switchgrass
Authors: Jensen Elaine , Shafiei Reza , Ma Xue‐Feng , Serba Desalegn D. , Smith Daniel P. , Slavov Gancho T. , Robson Paul , Farrar Kerrie , Thomas Jones Sian , Swaller Timothy , Flavell Richard , Clifton‐Brown John , Saha Malay C. , Donnison Iain 
Published: October 2020

AbstractFlowering in perennial species is directed via complex signalling pathways that adjust to developmental regulations and environmental cues. Synchronized flowering in certain environments is a prerequisite to commercial seed production, and so the elucidation of the genetic architecture of flowering time in Miscanthus and switchgrass could aid breeding in these underdeveloped species. In this context, we assessed a mapping population in Miscanthus and two ecologically diverse switchgrass mapping populations over 3 years from planting. Multiple flowering time quantitative trait loci (QTL) were identified in both species. Remarkably, the most significant Miscanthus and switchgrass QTL proved to be syntenic, located on linkage groups 4 and 2, with logarithm of odds scores of 17.05 and 21.8 respectively. These QTL regions contained three flowering time transcription factors: Squamosa Promoter‐binding protein‐Like, MADS‐box SEPELLATA2 and gibberellin‐responsive bHLH137. The former is emerging as a key component of the age‐related flowering time pathway.
HLA genotyping meets response to immune checkpoint inhibitors prediction: A story just started
Authors: Ivanova Milena , Shivarov Velizar 
Published: October 2020

AbstractThe implementation of the immune checkpoint blockade as a therapeutic option in contemporary oncology is one of the significant immunological achievements in the last century. Constantly accumulating evidence suggests that the response to immune checkpoint inhibitors (ICIs) is not universal. Therefore, it is critical to identify determinants for response, resistance and adverse effects of immune checkpoint therapy that could be developed as prognostic and predictive markers. Recent large scale analyses of cancer genome data revealed the key role of HLA class I and class II molecules in cancer immunoediting, and it appears that HLA diversity can predict response to ICIs. In the present review, we summarize the emerging data on the role of HLA germline variations as a marker for response to ICIs.
Experience with research paradigms relates to infants’ direction of preference
Authors: Santolin Chiara , Garcia‐Castro Gonzalo , Zettersten Martin , Sebastian‐Galles Nuria , Saffran Jenny R. 
Published: October 2020

AbstractInterpreting and predicting direction of preference in infant research has been a thorny issue for decades. Several factors have been proposed to account for familiarity versus novelty preferences, including age, length of exposure, and task complexity. The current study explores an additional dimension: experience with the experimental paradigm. We reanalyzed the data from 4 experiments on artificial grammar learning in 12‐month‐old infants run using the head‐turn preference procedure (HPP). Participants in these studies varied substantially in their number of laboratory visits. Results show that the number of HPP studies is related to direction of preference: Infants with limited experience with the HPP setting were more likely to show familiarity preferences than infants who had amassed more experience with this paradigm. This evidence has important implications for the interpretation of experimental results: Experience with a given method or, more broadly, with the laboratory environment may affect infants’ patterns of preferences.
Dynamic changes in numerical acuity in 4‐month‐old infants
Authors: Wang Jinjing (Jenny) , Feigenson Lisa 
Published: October 2020

AbstractPreverbal infants represent the approximate numerosity of visual and auditory arrays: By 6 months old, they reliably discriminate eight dots or tones from 16 (a 1:2 ratio), but not eight from 12 (a 2:3 ratio). The precision of this approximate number sense improves gradually over childhood and into adulthood. However, less is known about numerical abilities in younger infants, and in particular, whether there is developmental change in the number sense in the first half year of life. Here, in four experiments, we measured numerical precision in 4‐month‐old infants (N = 128) using a visual habituation task comparable to that in studies of older infants. We found that 4‐month‐olds exhibited poorer numerical discrimination than the 6‐month‐olds tested in previous studies, dishabituating to a 1:4 change in numerical ratio, but not a 1:3 change. Like older infants, 4‐month‐olds’ numerical precision improved when they were provided with redundant visual and auditory input; when both visual and auditory information were present, 4‐month‐olds discriminated a 1:3 but not a 1:2 ratio. These results suggest that Approximate Number System precision develops in early infancy and may be sensitive to intersensory redundancy as early as four months of age.
Blow to the Northeast? Intraspecific differentiation of Populus davidiana suggests a north‐eastward skew of a phylogeographic break in East Asia
Authors: Song Xinya , Milne Richard I. , Fan Xiaoyan , Xie Siyu , Zhang Lei , Zheng Honglei , Fan Liqiang , Chung Jae Min , Chung Myong Gi , Ma Tao , Xu Xiaoting , Wang Jing , Mao Kangshan 
Published: October 2020

AbstractAimThere is increasing interest in the role that biological traits, and historical and biogeographic processes, play in the formation of phylogeographic patterns. An arid belt that once existed in northern China might have affected many plants, but this has yet to be tested in an arid‐tolerant, wind‐dispersed species. Here, we tested how intrinsic and extrinsic factors have affected the phylogeography of Populus davidiana.LocationEast Asia.MethodsGenetic variation was surveyed across 40 populations (555 individuals) covering the Chinese range of P. davidiana, using 16 nuclear microsatellite loci (nSSRs) and four chloroplast fragments (cpDNA). Demographic and migration hypotheses were tested using coalescent‐based approaches, and the present and past potential distributions were predicted using species distribution modelling.ResultsMolecular data divide P. davidiana into two lineages, north‐eastern China (NECR) and central and northern China (CNCR); however, the dividing line is around 118ºE for nSSRs, but 122ºE for cpDNA. The range and habitat of the two lineages barely overlap at present, and their ecological separation may have initiated around the Pliocene‐Quaternary boundary, when major intraspecific cpDNA clades diverged. NECR and CNCR experienced post‐glacial north‐eastward and northward range shifts respectively. Bi‐directional historical gene flow was detected between NECR and CNCR for both bi‐parentally inherited nSSRs and maternally inherited cpDNA. Demographic inferences suggest a severe bottleneck for CNCR and especially NECR, around the latest Pleistocene.Main conclusionsThe phylogeographic break within P. davidiana reflects the impacts of biogeographic history, climate and biological traits. Its plumed, wind‐dispersed seeds might be especially significant because prevailing south‐western spring winds may have moved the NECR‐CNCR boundary further east than similar phylogenetic breaks in other species, and also moved the cpDNA boundary relative to that for nuclear markers. Biological traits, therefore, should also be considered when examining the genetic and ecological differentiation between closely related taxa.
The carboxy‐terminus of the human ARPKD protein fibrocystin can control STAT3 signalling by regulating SRC‐activation
Authors: Dafinger Claudia , Mandel Amrei M. , Braun Alina , Göbel Heike , Burgmaier Kathrin , Massella Laura , Mastrangelo Antonio , Dötsch Jörg , Benzing Thomas , Weimbs Thomas , Schermer Bernhard , Liebau Max C. 
Published: October 2020

AbstractAutosomal recessive polycystic kidney disease (ARPKD) is mainly caused by variants in the PKHD1 gene, encoding fibrocystin (FC), a large transmembrane protein of incompletely understood cellular function. Here, we show that a C‐terminal fragment of human FC can suppress a signalling module of the kinase SRC and signal transducer and activator of transcription 3 (STAT3). Consistently, we identified truncating genetic variants specifically affecting the cytoplasmic tail in ARPKD patients, found SRC and the cytoplasmic tail of fibrocystin in a joint dynamic protein complex and observed increased activation of both SRC and STAT3 in cyst‐lining renal epithelial cells of ARPKD patients.