bluuebunny/crossref_metadata_2025_split huggingface dataset:
I536T variant of RBM20 affects splicing of cardiac structural proteins that are causative for developing dilated cardiomyopathy
Authors: Yamamoto Takuma , Sano Rie , Miura Aya , Imasaka Mai , Naito Yoshiro , Nishiguchi Minori , Ihara Kensuke , Otani Naruhito , Kominato Yoshihiko , Ohmuraya Masaki , Kuroyanagi Hidehito , Nishio Hajime 
Published: October 2022

Abstract
RBM20 is one of the genes predisposing to dilated cardiomyopathy (DCM). Variants in the RS domain have been reported in many DCM patients, but the pathogenicity of variants within the RNA-recognition motif remains unknown. Two human patients with the I536T-RBM20 variant without an apparent DCM phenotype were identified in sudden death cohorts. A splicing reporter assay was performed, and an I538T knock-in mouse model (Rbm20I538T) was generated to determine the significance of this variant. The reporter assay demonstrated that the human I536T variant affected the TTN splicing pattern compared to wild-type. In the mouse experiments, Rbm20I538T mice showed different splicing patterns in Ttn, Ldb3, Camk2d, and Ryr2. The expressions of Casq1, Mybpc2, and Myot were upregulated in Rbm20I538T mice, but Rbm20I538T mice showed neither DCM nor cardiac dysfunction on histopathological examination and ultrasound echocardiography. The I536T-RBM20 (I538T-Rbm20) variant changes gene splicing and affects gene expression, but the splicing and expression changes in Ttn and Ca handling genes such as Casq1, Camk2d, and Ryr2 do not cause DCM morphology in the mouse model.

Key messages
• Two human patients with the I536T-RBM20 variant without a DCM phenotype were identified.
• A splicing reporter assay demonstrated that the variant affected the TTN splicing.
• Rbm20I538T mice showed neither DCM nor cardiac dysfunction.
• Rbm20I538T mice showed different splicing patterns and the gene expressions.
Quantifying the utility of islet autoantibody levels in the prediction of type 1 diabetes in children
Authors: Ng Kenney , Anand Vibha , Stavropoulos Harry , Veijola Riitta , Toppari Jorma , Maziarz Marlena , Lundgren Markus , Waugh Kathy , Frohnert Brigitte I. , Martin Frank , Lou Olivia , Hagopian William , Achenbach Peter ,   for the T1DI Study Group
Published: October 2022

Abstract
Aims/hypothesis
The aim of this study was to explore the utility of islet autoantibody (IAb) levels for the prediction of type 1 diabetes in autoantibody-positive children.

Methods
Prospective cohort studies in Finland, Germany, Sweden and the USA followed 24,662 children at increased genetic or familial risk of developing islet autoimmunity and diabetes. For the 1403 who developed IAbs (523 of whom developed diabetes), levels of autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated antigen-2 (IA-2A) were harmonised for analysis. Diabetes prediction models using multivariate logistic regression with inverse probability censored weighting (IPCW) were trained using 10-fold cross-validation. Discriminative power for disease was estimated using the IPCW concordance index (C index) with 95% CI estimated via bootstrap.

Results
A baseline model with covariates for data source, sex, diabetes family history, HLA risk group and age at seroconversion with a 10-year follow-up period yielded a C index of 0.61 (95% CI 0.58, 0.63). The performance improved after adding the IAb positivity status for IAA, GADA and IA-2A at seroconversion: C index 0.72 (95% CI 0.71, 0.74). Using the IAb levels instead of positivity indicators resulted in even better performance: C index 0.76 (95% CI 0.74, 0.77). The predictive power was maintained when using the IAb levels alone: C index 0.76 (95% CI 0.75, 0.76). The prediction was better for shorter follow-up periods, with a C index of 0.82 (95% CI 0.81, 0.83) at 2 years, and remained reasonable for longer follow-up periods, with a C index of 0.76 (95% CI 0.75, 0.76) at 11 years. Inclusion of the results of a third IAb test added to the predictive power, and a suitable interval between seroconversion and the third test was approximately 1.5 years, with a C index of 0.78 (95% CI 0.77, 0.78) at 10 years follow-up.

Conclusions/interpretation
Consideration of quantitative patterns of IAb levels improved the predictive power for type 1 diabetes in IAb-positive children beyond qualitative IAb positivity status.

Graphical abstract
Degeneration of natural Lagrangians and Prymian integrable systems
Authors: Franco Emilio 
Published: October 2022

AbstractStarting from an anti-symplectic involution on a K3 surface, one can consider a natural Lagrangian subvariety inside the moduli space of sheaves over the K3. One can also construct a Prymian integrable system following a construction of Markushevich–Tikhomirov, extended by Arbarello–Saccà–Ferretti, Matteini and Sawon–Shen. In this article we address a question of Sawon, showing that these integrable systems and their associated natural Lagrangians degenerate, respectively, into fix loci of involutions considered by Heller–Schaposnik, García-Prada–Wilkin and Basu–García-Prada. Along the way we find interesting results such as the proof that the Donagi–Ein–Lazarsfeld degeneration is a degeneration of symplectic varieties, a generalization of this degeneration, originally described for K3 surfaces, to the case of an arbitrary smooth projective surface, and a description of the behaviour of certain involutions under this degeneration.
Investigation of native and aggregated therapeutic proteins in human plasma with asymmetrical flow field-flow fractionation and mass spectrometry
Authors: Ramm Ingrid , Leeman Mats , Schagerlöf Herje , León Ileana Rodríguez , Castro Alejandra , Nilsson Lars 
Published: October 2022

AbstractPhysiochemical degradation of therapeutic proteins in vivo during plasma circulation after administration can have a detrimental effect on their efficacy and safety profile. During drug product development, in vivo animal studies are necessary to explore in vivo protein behaviour. However, these studies are very demanding and expensive, and the industry is working to decrease the number of in vivo studies. Consequently, there is considerable interest in the development of methods to pre-screen the behaviour of therapeutic proteins in vivo using in vitro analysis. In this work, asymmetrical flow field-flow fractionation (AF4) and liquid chromatography–mass spectrometry (LC-MS) were combined to develop a novel analytical methodology for predicting the behaviour of therapeutic proteins in vivo. The method was tested with two proteins, a monoclonal antibody and a serum albumin binding affibody. After incubation of the proteins in plasma, the method was successfully used to investigate and quantify serum albumin binding, analyse changes in monoclonal antibody size, and identify and quantify monoclonal antibody aggregates.
Graphical abstract
Rank change and growth within social hierarchies of the orange clownfish, Amphiprion percula
Authors: Fitzgerald L. M. , Harrison H. B. , Coker D. J. , Sáenz-Agudelo P. , Srinivasan M. , Majoris J. E. , Boström Einarsson L. , Pujol B. , Bennett-Smith M. , Thorrold S. R. , Planes S. , Jones G. P. , Berumen M. L. 
Published: October 2022

AbstractSocial hierarchies within groups define the distribution of resources and provide benefits that support the collective group or favor dominant members. The progression of individuals through social hierarchies is a valuable characteristic for quantifying population dynamics. On coral reefs, some clownfish maintain size-based hierarchical communities where individuals queue through social ranks. The cost of waiting in a lower-ranked position is outweighed by the reduced risk of eviction and mortality. The orange clownfish, Amphiprion percula, maintains stable social groups with subordinate individuals queuing to be part of the dominant breeding pair. Strong association with their host anemone, complex social interactions, and relatively low predation rates make them ideal model organisms to assess changes in group dynamics through time in their natural environment. Here, we investigate the rank changes and isometric growth rates of A. percula from 247 naturally occurring social groups in Kimbe Island, Papua New Guinea (5° 12′ 13.54″ S, 150° 22′ 32.69″ E). We used DNA profiling to assign and track individuals over eight years between 2011 and 2019. Over half of the individuals survived alongside two or three members of their original social group, with twelve breeding pairs persisting over the study period. Half of the surviving individuals increased in rank and experienced double the growth rate of those that maintained their rank. Examining rank change in a wild fish population provides new insights into the complex social hierarchies of reef fishes and their role in social evolution.
Rapid growth of antimicrobial resistance: the role of agriculture in the problem and the solutions
Authors: Stanley Dragana , Batacan Romeo , Bajagai Yadav Sharma 
Published: October 2022

Abstract
The control of infectious diseases has always been a top medical priority. For years during the so-called antibiotic era, we enjoyed prolonged life expectancy and the benefits of superior pathogen control. The devastating failure of the medical system, agriculture and pharmaceutical companies and the general population to appreciate and safeguard these benefits is now leading us into a grim post-antibiotic era. Antimicrobial resistance (AMR) refers to microorganisms becoming resistant to antibiotics that were designed and expected to kill them. Prior to the COVID-19 pandemic, AMR was recognised by the World Health Organization as the central priority area with growing public awareness of the threat AMR now presents. The Review on Antimicrobial Resistance, a project commissioned by the UK government, predicted that the death toll of AMR could be one person every 3 seconds, amounting to 10 million deaths per year by 2050. This review aims to raise awareness of the evergrowing extensiveness of antimicrobial resistance and identify major sources of this adversity, focusing on agriculture’s role in this problem and its solutions.

Keypoints
• Widespread development of antibiotic resistance is a major global health risk.
• Antibiotic resistance is abundant in agricultural produce, soil, food, water, air and probiotics.
• New approaches are being developed to control and reduce antimicrobial resistance.
Area Quasi-minimizing Partitions with a Graphical Constraint: Relaxation and Two-Dimensional Partial Regularity
Authors: Bonacini Marco , Cristoferi Riccardo 
Published: October 2022

AbstractWe consider a variational model for periodic partitions of the upper half-space into three regions, where two of them have prescribed volume and are subject to the geometric constraint that their union is the subgraph of a function, whose graph is a free surface. The energy of a configuration is given by the weighted sum of the areas of the interfaces between the different regions and a general volume-order term. We establish existence of minimizing configurations via relaxation of the energy involved, in any dimension. Moreover, we prove partial regularity results for volume-constrained minimizers in two space dimensions. Thin films of diblock copolymers are a possible application and motivation for considering this problem.
Assessment of PABPN1 nuclear inclusions on a large cohort of patients and in a human xenograft model of oculopharyngeal muscular dystrophy
Authors: Roth Fanny , Dhiab Jamila , Boulinguiez Alexis , Mouigni Hadidja-Rose , Lassche Saskia , Negroni Elisa , Muraine Laura , Marhic Alix , Oliver Alison , Lainé Jeanne , Rouche Andrée , O’Ferrall Erin K. , van Engelen Baziel , Ottenheijm Coen , Greif Hagar , Blumen Sergiu , Lacau St Guily Jean , Perie Sophie , Butler-Browne Gillian , Mouly Vincent , Trollet Capucine 
Published: October 2022

AbstractOculopharyngeal muscular dystrophy (OPMD) is a rare muscle disease characterized by an onset of weakness in the pharyngeal and eyelid muscles. The disease is caused by the extension of a polyalanine tract in the Poly(A) Binding Protein Nuclear 1 (PABPN1) protein leading to the formation of intranuclear inclusions or aggregates in the muscle of OPMD patients. Despite numerous studies stressing the deleterious role of nuclear inclusions in cellular and animal OPMD models, their exact contribution to human disease is still unclear. In this study, we used a large and unique collection of human muscle biopsy samples to perform an in-depth analysis of PABPN1 aggregates in relation to age, genotype and muscle status with the final aim to improve our understanding of OPMD physiopathology. Here we demonstrate that age and genotype influence PABPN1 aggregates: the percentage of myonuclei containing PABPN1 aggregates increases with age and the chaperone HSP70 co-localize more frequently with PABPN1 aggregates with a larger polyalanine tract. In addition to the previously described PRMT1 and HSP70 co-factors, we identified new components of PABPN1 aggregates including GRP78/BiP, RPL24 and p62. We also observed that myonuclei containing aggregates are larger than myonuclei without. When comparing two muscles from the same patient, a similar amount of aggregates is observed in different muscles, except for the pharyngeal muscle where fewer aggregates are observed. This could be due to the peculiar nature of this muscle which has a low level of PAPBN1 and contains regenerating fibers. To confirm the fate of PABPN1 aggregates in a regenerating muscle, we generated a xenograft model by transplanting human OPMD muscle biopsy samples into the hindlimb of an immunodeficient mouse. Xenografts from subjects with OPMD displayed regeneration of human myofibers and PABPN1 aggregates were rapidly present—although to a lower extent-after muscle fiber regeneration. Our data obtained on human OPMD samples add support to the dual non-exclusive models in OPMD combining toxic PABPN1 intranuclear inclusions together with PABPN1 loss of function which altogether result in this late-onset and muscle selective disease.
3D segmentation of dental crown for volumetric age estimation with CBCT imaging
Authors: Merdietio Boedi Rizky , Shepherd Simon , Oscandar Fahmi , Mânica Scheila , Franco Ademir 
Published: October 2022

Abstract
In adult dental age estimation, segmentation of dental volumetric information from different tooth parts using cone-beam computed tomography (CBCT) has proven beneficial in improving the regression model reliability. This segmentation method can be expanded in the crown part since the volumetric information in the crown is affected by attrition in the enamel and secondary dentine in the dentine and pulp chamber. CBCT scans from 99 patients aged between 20 and 60 were collected retrospectively. A total of 80 eligible teeth for each tooth type were used in this study. The enamel to dentine volume ratio (EDVR), pulp to dentine volume ratio (PDVR) and sex were used as independent variables to predict chronological age (CA). The EDVR was not affected by PDVR. The highest R2 was calculated from the maxillary canine (R2 = 0.6). The current approach in crown segmentation has proven to improve model performance in anterior maxillary teeth.
A validated Screening instrument for Child Abuse and Neglect (SCAN) at the emergency department
Authors: Hoedeman F. , Puiman P. J. , van den Heuvel E. A. L. , Affourtit M. J. , Bakx R. , Langendam M. W. , van de Putte E. M. , Russel-Kampschoer I. M. B. , Schouten M. C. M. , Teeuw A. H. , de Koning H. J. , Moll H. A. 
Published: October 2022

AbstractThe objective of this study is to develop and validate a screening instrument for the recognition of child maltreatment in the emergency department (ED). Existing data on screening questions and outcomes (diagnosis of child maltreatment) from three large observational screening studies at eight different EDs in the Netherlands were harmonized. A multivariate logistic regression was performed to develop the Screening instrument for Child Abuse and Neglect (SCAN). The SCAN was validated by performing a cross-validation and calculating the discriminative ability. A total of 24,963 patients were included. Out of the potential screening questions the following questions were included in the final instrument: is the injury compatible with the history, and does it correspond to the child’s developmental level? (aOR 10.40, 95% CI 5.69–19.02), was there an unnecessary delay in seeking medical help? (aOR 3.45, 95% CI 1.73–6.88) and is the behaviour/interaction of the child and parents (carers) appropriate? (aOR 14.67, 95% CI 7.93–27.13). The SCAN had a pooled AUC of 0.75 (95% CI 0.63–0.87) in the cross-validation. The question “Are there other signals that make you doubt the safety of the child and/or family?” (available in only one of the original datasets, OR 182.9; 95% CI 102.3–327.4) was by consensus added to the final SCAN.Conclusion: This validated and brief Screening instrument for Child Abuse and Neglect (SCAN) is designed to improve early recognition of child maltreatment in the ED. A positive screening result of the SCAN warrants a thorough work-up for child maltreatment, including a top-toe examination, if necessary additional diagnostics and adequate safety measures.

What is Known:• Screening instruments increase the detection of possible cases of child maltreatment in the emergency department and support health care professionals to identify these cases.• The application of different screening instruments led to the need for one brief validated instrument.

What is New:• This study presents a validated and brief Screening instrument for Child Abuse and Neglect (SCAN), consisting of four questions.• The SCAN supports professionals in detecting signals of child maltreatment, and a positive screening result should lead to a thorough work-up, including a top-toe examination, complete history, additional diagnostic tests and consultation of a child abuse expert.
Functional morphology of prey capture in stream-dwelling sailfin silversides (Telmatherinidae) based on high-speed video recordings
Authors: Wasiljew Benjamin D. , Pfaender Jobst , Wipfler Benjamin , Wantania Letha Louisiana , Herder Fabian 
Published: October 2022

AbstractUnderstanding how ecology shapes the evolution of morphological traits is a major goal in organismal biology. By quantifying force of motion, hypotheses on the function of fundamental tasks of animals like feeding can be tested. Ray-finned fishes use various feeding strategies, classified into three main feeding modes: suction, ram and manipulation. While manipulation feeders are usually distinct in morphology and feeding behavior, differentiation between suction and ram feeders is often fine-scaled and transitional. Previous studies have identified different feeding modes and biomechanical adaptations on interspecific and intersexual levels in lake-dwelling sailfin silversides, species of a Sulawesi freshwater radiation. Functional feeding morphology of stream-dwelling species remained in contrast unstudied. We hypothesized that different requirements of riverine habitats favor the evolution of alternative functional adaptations in stream-dwelling sailfin silversides. To test this hypothesis, we investigated feeding of two phenotypically distinct riverine species, Telmatherina bonti and Marosatherina ladigesi, and their sexes, by high-speed videos and biomechanical models. The kinematic approaches identify T. bonti as ram feeder and M. ladigesi as suction feeder. Surprisingly, the biomechanical models of the jaw apparatus provide contradicting results: only one out of three studied parameters varies between both species. Contrarily to lake-dwelling Telmatherina, sexes of both species do not differ in feeding biomechanics. We conclude that T. bonti predominantly uses ram feeding while M. ladigesi primarily uses suction feeding as its main hunting strategy. Feeding biomechanics of stream-dwelling sailfin silversides are less distinct compared to lake-dwelling species, likely due to different trophic ecologies or less stable ecological conditions.
Public and patient perceptions of diagnostic labels for non-specific low back pain: a content analysis
Authors: O’Keeffe Mary , Michaleff Zoe A. , Harris Ian A. , Buchbinder Rachelle , Ferreira Giovanni E. , Zadro Joshua R. , Traeger Adrian C. , Thomas Rae , Belton Joletta , Darlow Ben , Maher Chris G. 
Published: October 2022

Abstract
Purpose
An online randomised experiment found that the labels lumbar sprain, non-specific low back pain (LBP), and episode of back pain reduced perceived need for imaging, surgery and second opinions compared to disc bulge, degeneration, and arthritis among 1447 participants with and without LBP. They also reduced perceived seriousness of LBP and increased recovery expectations.

Methods
In this study we report the results of a content analysis of free-text data collected in our experiment. We used two questions: 1. When you hear the term [one of the six labels], what words or feelings does this make you think of? and 2. What treatment (s) (if any) do you think a person with [one of the six labels] needs? Two independent reviewers analysed 2546 responses.

Results
Ten themes emerged for Question1. Poor prognosis emerged for disc bulge, degeneration, and arthritis, while good prognosis emerged for lumbar sprain, non-specific LBP, and episode of back pain. Thoughts of tissue damage were less common for non-specific LBP and episode of back pain. Feelings of uncertainty frequently emerged for non-specific LBP. Twenty-eight treatments emerged for Question2. Surgery emerged for disc bulge, degeneration, and arthritis compared to lumbar sprain, non-specific LBP, and episode of back pain. Surgery did not emerge for non-specific LBP and episode of back pain.

Conclusion
Our results suggest that clinicians should consider avoiding the labels disc bulge, degeneration and arthritis and opt for labels that are associated with positive beliefs and less preference for surgery, when communicating with patients with LBP.
Crystal growth, crystal structure determination, and computational studies of a new mixed (NH4)2Mn1–xZnx(SO4)2(H2O)6 Tutton salt
Authors: Neto João G. Oliveira , Viana Jailton R. , Lopes Jardel B. O. , Lima Antonio D. S. G. , Sousa Marcus L. , Lage Mateus R. , Stoyanov Stanislav R. , Lang Rossano , Santos Adenilson O. 
Published: October 2022

AbstractTutton salts have been extensively explored in recent decades due to their attractive physical and chemical properties, which make them potential candidates for thermochemical heat storage systems and optical technologies. In this paper, a series of new mixed Tutton salts with the chemical formula (NH4)2Mn1–xZnx(SO4)2(H2O)6 is reported. Crystals are successfully grown by the solvent slow evaporation method and characterized by powder X-ray diffraction (PXRD) with Rietveld refinement. In particular, the crystal structure of the mixed (NH4)2Mn0.5Zn0.5(SO4)2(H2O)6 crystal is solved through PRXD data using the DICVOL06 algorithm for diffraction pattern indexing and the Le Bail method for lattice parameter and spatial group determination. The structure is refined using the Rietveld method implemented in TOPAS® and reported in the Cambridge Structural Database file number 2104098. Moreover, a computational study using Hirshfeld surface and crystal void analyses is conducted to identify and quantify the intermolecular interactions in the crystal structure as well as to determine the amount of free space in the unit cell. Furthermore, 2D-fingerprint plots are generated to evaluate the main intermolecular contacts that stabilize the crystal lattice. Density functional theory is employed to calculate the structural, thermodynamic, and electronic properties of the coordination [Zn(H2O)6]2+ and [Mn(H2O)6]2+ complexes present in the salts. Molecular orbitals, bond lengths, and the Jahn–Teller effect are also discussed. The findings suggest that in Mn-Zn salts several properties dependent on the electronic structure can be tuned up by modifying the chemical composition.