bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to proceed after “negative” exome: A review on genetic diagnostics, limitations, challenges, and emerging new multiomics techniques
Authors: Wortmann Saskia B. , Oud Machteld M. , Alders Mariëlle , Coene Karlien L. M. , van der Crabben Saskia N. , Feichtinger René G. , Garanto Alejandro , Hoischen Alex , Langeveld Mirjam , Lefeber Dirk , Mayr Johannes A. , Ockeloen Charlotte W. , Prokisch Holger , Rodenburg Richard , Waterham Hans R. , Wevers Ron A. , van de Warrenburg Bart P. C. , Willemsen Michel A. A. P. , Wolf Nicole I. , Vissers Lisenka E. L. M. , van Karnebeek Clara D. M. 
Published: May 2022

AbstractExome sequencing (ES) in the clinical setting of inborn metabolic diseases (IMDs) has created tremendous improvement in achieving an accurate and timely molecular diagnosis for a greater number of patients, but it still leaves the majority of patients without a diagnosis. In parallel, (personalized) treatment strategies are increasingly available, but this requires the availability of a molecular diagnosis. IMDs comprise an expanding field with the ongoing identification of novel disease genes and the recognition of multiple inheritance patterns, mosaicism, variable penetrance, and expressivity for known disease genes. The analysis of trio ES is preferred over singleton ES as information on the allelic origin (paternal, maternal, “de novo”) reduces the number of variants that require interpretation. All ES data and interpretation strategies should be exploited including CNV and mitochondrial DNA analysis. The constant advancements in available techniques and knowledge necessitate the close exchange of clinicians and molecular geneticists about genotypes and phenotypes, as well as knowledge of the challenges and pitfalls of ES to initiate proper further diagnostic steps. Functional analyses (transcriptomics, proteomics, and metabolomics) can be applied to characterize and validate the impact of identified variants, or to guide the genomic search for a diagnosis in unsolved cases. Future diagnostic techniques (genome sequencing [GS], optical genome mapping, long‐read sequencing, and epigenetic profiling) will further enhance the diagnostic yield. We provide an overview of the challenges and limitations inherent to ES followed by an outline of solutions and a clinical checklist, focused on establishing a diagnosis to eventually achieve (personalized) treatment.
Which test is the best? An updated literature review of imaging modalities for acute ankle diastasis injuries
Authors: Ng Nico , Onggo James Randolph , Nambiar Mithun , Maingard Julian Tam , Ng David , Gupta Gaurav , Nandurkar Dee , Babazadeh Sina , Bedi Harvinder 
Published: May 2022

AbstractAnkle diastasis injuries, or ankle syndesmotic injuries, are common among athletes who usually experience a traumatic injury to the ankle. Long‐term complications are avoidable when these injuries are diagnosed promptly and accurately treated. Whilst ankle arthroscopy remains the gold standard diagnostic modality for ankle diastasis injuries, imaging modalities are still widely utilised due to the treatment having greater accessibility, being less invasive and the most cost effective. There are various imaging modalities used to diagnose diastasis injuries, varying in levels of specificity and sensitivity. These observation methods include; X‐ray, computed tomography (CT), magnetic resonance imaging (MRI) and ankle arthroscopy. This article uncovers common criteria and parameters to diagnose diastasis injuries through the implementation of different imaging modalities. The conclusions addressed within this article are deduced from a total of 338 articles being screened with only 43 articles being selected for the purposes of this examination. Across most articles, it was concluded that that plain X‐ray should be used in the first instance due to its wide availability, quick processing time, and low cost. CT is the next recommended investigation due to its increased sensitivity and specificity, ability to show the positional relationship of the distal tibiofibular syndesmosis, and reliability in detecting minor diastasis injuries. MRI is recommended when ankle diastasis injuries are suspected, but not diagnosed on previous imaging modalities. It has the highest sensitivity and specificity compared to X‐ray and CT.
Decoupled abiotic and biotic drivers of aboveground and topsoil organic carbon stocks in temperate forests
Authors: Kazempour Larsary Maryam , Pourbabaei Hassan , Salehi Ali , Yousefpour Rasoul , Ali Arshad 
Published: May 2022

AbstractForests are major components of global carbon (C) cycling, and hence, it is crucial to explore the drivers of forest functions related to C sequestration. Here, using the multiple linear regression models (MLMs) and structural equation models (SEMs), we evaluated how abiotic (i.e., soil nutrients and topography) and biotic [i.e., functional trait diversity (FTD) and functional trait identity (FTI)] factors regulate aboveground C (AGC) and topsoil (0–30 cm) organic C (SOC) stocks across 104 plots in temperate forests of Northern Iran. The optimal MLMs showed that the community‐weighted mean (CWM) of wood density and functional divergence increased, but functional evenness decreased AGC stock, where FTI values contributed much (i.e., 74.40%) to the explained variance in AGC stock as compared to FTD indices (12.86%) and abiotic factors (12.74%). On contrary, SOC stock was mainly promoted by soil‐available phosphorus, where abiotic factors contributed much (92.62%) to the explained variance as compared to FTD indices (6.73%) and FTI values (0.65%). The final best‐fitted SEMs showed that AGC stock was strongly controlled (β = 0.64) by FTI values (i.e., a latent variable of CWM of wood density and plant maximum height), whereas SOC stock was strongly controlled (β = 0.74) by abiotic factors (i.e., a latent variable of soil‐available phosphorus and total nitrogen). We argue that suitable functional strategies in combination with soil nutrients should be taken into priority during the forestland management and policy plans for the improvement of C stocks in above‐ and belowground compartments of forest ecosystems.
Spatial–temporal dynamics and recovery mechanisms of dried soil layers under Robinia pseudoacacia forest based on in‐situ field data from 2017 to 2020
Authors: He Meina , Wang Yunqiang , Wang Li , Jia Xiaoxu , Zhao Chunlei , Zhang Pingping 
Published: May 2022

AbstractPlanting Robinia pseudoacacia in water‐limited regions can promote soil and water conservation and ecological service functions. However, it can cause the formation of below ground dried soil layers (DSLs), causing land degradation and tree mortality. To ascertain the spatial–temporal dynamics and recovery processes of DSLs, we monitored the deep soil water content (SWC) to a depth of 500 cm at 27 sites on a typical R. pseudoacacia forest from 2017 to 2020 and calculated the evaluation indices of DSLs based on plant‐available SWC (PASWC) and stable field capacity (SFC). Compared with PASWC‐identified DSLs, the degree of SFC‐identified DSLs was more severe, although the spatial–temporal characteristics were similar. Severe soil desiccation was identified as 79% of the 500 cm profile dried out below 101 cm. The mean thickness of DSL and mean SWC within a DSL were 396 cm and 9.0%, respectively, and the quantitative index reached Grade III (severe) DSLs. All DSL indices demonstrated weak or moderate variability in space and strong variability in time. The heterogeneity of rainfall events and microtopographic positions explain the spatial–temporal variation of DSL indices well. A heavy rainfall event (>50 mm) triggered the disappearance of DSLs at some sites, indicating the possibility of DSLs recovery based on field observations under natural condition. Microtopography (such as the swales) provides advantageous conditions to the recovery of DSLs by redistributing rainfall flow at the local scale. These results provide insights into DSLs recovery, which is useful for land development and rehabilitation in planted forests.
Continuity of daily temperature time series in the transition from conventional to automated stations for the Colombian coffee network
Authors: Ramírez Carabalí Carolina , Sarmiento Herrera Ninibeth Gibelli , Imbachi Quinchua Luis Carlos , García López Juan Carlos 
Published: May 2022

AbstractThe transition from conventional weather stations (CWSs) to automated weather stations (AWSs) of the Colombian coffee network has required testing their performance and adjusting the temperature measurements to ensure the continuity of the historical CWS series. In this study, the mean (Tmean), minimum (Tmin), and maximum temperature (Tmax) measurements of CWS and AWS operating in parallel at 36 locations between 2014 and 2019 were compared, and the biases of the daily temperature differences (CWS − AWS), the agreement index (d), and the percentage of data within the allowed range (PR05) were calculated. The most consistent method for calculating Tmean and Tmax for CWS was selected for use on the AWS data. With the standard normal homogeneity test and with the metadata, we found that the series of temperature differences between CWS and AWS was not homogeneous, instrument failures and sensor changes being the main causes of the lack of homogeneity. The statistical analyses indicated that the AWS data need to be adjusted to be continuous with the CWS series. To correct the temperature bias, two approaches were applied: quantile mapping and the additive constant. The results suggest that the quantile mapping adjustments improve the average bias at all stations but do not necessarily bring the percentage to within ±0.5°C. In Tmin and Tmean, 12 AWSs can give continuity with the historical series of the CWS, and for the rest of the stations and variables, the series of the AWSs are independent of the CWSs.
Comparison of strength testing modalities in dysferlinopathy
Authors: Reash Natalie F. , James Meredith K. , Alfano Lindsay N. , Mayhew Anna G. , Jacobs Marni , Iammarino Megan A. , Holsten Scott , Sakamoto Chikako , Tateishi Takayuki , Yajima Hiroyuki , Duong Tina , de Wolf Brittney , Gee Richard , Bharucha‐Goebel Diana X. , Bravver Elena , Mori‐Yoshimura Madoka , Bushby Kate , Rufibach Laura E. , Straub Volker , Lowes Linda P. ,   for the Jain COS Consortium
Published: May 2022

AbstractIntroduction/AimsDysferlinopathy demonstrates heterogeneity in muscle weakness between patients, which can progress at different rates over time. Changing muscle strength due to disease progression or from an investigational product is associated with changing functional ability. The purpose of this study was to compare three methods of strength testing used in the Clinical Outcome Study (COS) for dysferlinopathy to understand which method and which muscle groups were most sensitive to change over time.MethodsPatients were evaluated at each study visit using functional scales, manual muscle testing, and handheld dynamometry (HHD) at all 15 sites. A fixed‐frame system (Fixed) was used at a subset of seven sites. Screening and baseline visits were evaluated for reliability. Data over a 1‐year period were analyzed to determine sensitivity to change among strength modalities and individual muscle groups.ResultsHHD and Fixed captured significant change across 1 year in summed muscle strength score of four muscle groups (P < .01). Strength summed scores were significantly correlated with functional scales (rho = 0.68‐0.92, P < .001). Individual muscle groups, however, showed high levels of variability between visits.DiscussionAlthough both HHD and Fixed demonstrate change over 12 months, HHD is a less expensive option that provides data on a continuous scale and may be easier to implement. Due to variability in strength measures, researchers should carefully consider use of strength testing as an outcome and may wish to select functional measures with less variability as clinical trial endpoints.
Quasistatic fracture using nonlinear‐nonlocal elastostatics with explicit tangent stiffness matrix
Authors: Diehl Patrick , Lipton Robert 
Published: May 2022

AbstractWe apply a nonlinear‐nonlocal field theory for numerical calculation of quasistatic fracture. The model is given by a regularized nonlinear pairwise potential in a peridynamic formulation. The potential function is given by an explicit formula with an explicit first and second derivatives. This fact allows us to write the entries of the tangent stiffness matrix explicitly thereby saving computational costs during the assembly of the tangent stiffness matrix. We validate our approach against classical continuum mechanics for the linear elastic material behavior. In addition, we compare our approach to a state‐based peridynamic model that uses standard numerical derivations to assemble the tangent stiffness matrix. The numerical experiments show that for elastic material behavior our approach agrees with both classical continuum mechanics and the state‐based model. The fracture model is applied to produce a fracture simulation for a ASTM E8 like tension test. We conclude with an example of crack growth in a pre‐cracked square plate. For the pre‐cracked plate, we investigated load in force (soft loading) and load in displacement (hard loading). Our approach is novel in that only bond softening is used as opposed to bond breaking. For the fracture simulation we have shown that our approach works with and without initial damage for two common test problems.
Prenatal diagnosis of Cornelia de Lange syndrome from 12 to 17 weeks' gestation
Authors: Wu Ting , Chen Jiao 
Published: May 2022

Key pointsWhat's already known about this topic?

The earliest reported prenatal ultrasound findings of facial features in Cornelia de Lange syndrome (CdLS) were before 20 weeks of gestation.

What does this study add?

This study showed the typical facial and head features of CdLS, including a smooth long philtrum and thin upper lip, a small upturned nose and anteverted nostrils, low‐set ears, and retrognathia. Recognizing the specific facial features of CdLS on two‐dimensional and three‐dimensional ultrasound is possible in the early second trimester.
Does plasma jet sintering follow an Arrhenius‐type expression?
Authors: Turan Nazli , Saeidi‐Javash Mortaza , Zhang Yanliang , Go David B. 
Published: May 2022

AbstractAtmospheric pressure, ambient temperature plasma jets have become a promising candidate for material processing in parallel with developments in additive manufacturing. Recent work has shown that plasma jets can be used to sinter printed nanoparticles at temperatures much lower than typically required for conventional thermal sintering. Here, we conduct a mechanistic study on plasma jet sintering that correlates specific energy input with the electrical conductivity of printed silver films after sintering. Increasing the specific energy input accelerated the sintering process following an Arrhenius‐like exponential trend across a large range of conditions, including both helium and argon plasma jets. Although an exponential relationship is also found with the plasma heated substrate temperature, independent studies indicate that heating is not the primary mechanism. These results suggest there is a general behavior that couples the plasma jet with the surface.
Exploration of quantitative site‐specific serum O‐glycoproteomics with isobaric labeling for the discovery of putative O‐glycoprotein biomarkers
Authors: Zhang Zihan , Xu Hua , Tian Zhixin 
Published: May 2022

AbstractPurposeExploration study of site‐specific isobaric‐TMT‐labeling quantitative serum O‐glycoproteomics for the discovery of putative O‐glycoprotein cancer biomarkers.Experimental designSera of 10 breast cancer patients was used as the exploration cohort. More abundant N‐glycosylation was first removed with PNGase F. After tryptic digestion of de‐N‐glycosylated serum proteome, the TMT‐labeled O‐glycopeptides mixture was prepared and analyzed with RPLC‐MS/MS. Site‐specific qualitative and quantitative database search of O‐glycopeptides was carried out with pGlyco 3.0. The same raw datasets were also searched with intact N‐glycopeptide search engine GPSeeker to exclude possible interference of N‐glycosylation. The final IDs were checked manually with GlcNAc‐containing glycosite‐determining fragment ions for confirmation.ResultsWith the control of spectrum‐level FDR ≤ 1% and manual validation, 299 O‐glycopeptides corresponding to 83 O‐glycosites and 66 O‐glycoproteins were identified, and 13 O‐glycopeptides were found differentially expressed. Most interestingly, differential O‐glycosylation was observed for IgG1 and IgG3, which is an interesting putative biomarker panel.Conclusion and clinical relevanceIsobaric‐labeling site‐specific quantitative O‐glycoproteomics is currently a state‐of‐the‐art instrumental platform for discovery of putative seral cancer biomarkers. Differential seral O‐glycosylation was observed in the IgG1 and IgG3.
Development and application of a pediatric mechanistic kidney model
Authors: Salem Farzaneh , Small Ben G. , Johnson Trevor N. 
Published: May 2022

AbstractPediatric physiologically‐based pharmacokinetic (P‐PBPK) models have been used to predict age related changes in the pharmacokinetics (PKs) of renally cleared drugs mainly in relation to changes in glomerular filtration rate. With emerging data on ontogeny of renal transporters, mechanistic models of renal clearance accounting for the role of active and passive secretion should be developed and evaluated. Data on age‐related physiological changes and ontogeny of renal transporters were applied into a mechanistic kidney within a P‐PBPK model. Plasma concentration–time profile and PK parameters of cimetidine, ciprofloxacin, metformin, tenofovir, and zidovudine were predicted in subjects aged 1 day to 18 years. The predicted and observed plasma concentration–time profiles and PK parameters were compared. The predicted concentration–time profile means and 5th and 95th percent intervals generally captured the observed data and variability in various studies. Overall, based on drugs and age bands, predicted to observed clearance were all within two‐fold and in 11 of 16 cases within 1.5‐fold. Predicted to observed area under the curve (AUC) and maximum plasma concentration (Cmax) were within two‐fold in 12 of 14 and 12 of 15 cases, respectively. Predictions in neonates and early infants (up to 14 weeks postnatal age) were reasonable with 15–20 predicted PK parameters within two‐fold of the observed. ciprofloxacin but not zidovudine PK predictions were sensitive to basal kidney uptake transporter ontogeny. The results indicate that a mechanistic kidney model accounting for physiology and ontogeny of renal processes and transporters can predict the PK of renally excreted drugs in children. Further data especially in neonates are required to verify the model and ontogeny profiles.
Evaluation of drug–drug interaction potential for pemigatinib using physiologically based pharmacokinetic modeling
Authors: Ji Tao , Chen Xuejun , Yeleswaram Swamy 
Published: May 2022

AbstractPemigatinib is a potent inhibitor of fibroblast growth factor receptor being developed for oncology indications. It is primarily metabolized by cytochrome P450 (CYP) 3A4, and the ratio of estimated concentration over concentration required for 50% inhibition ratio for pemigatinib as an inhibitor of P‐glycoprotein (P‐gp), organic cation transporter‐2 (OCT2), and multidrug and toxin extrusion protein‐1 (MATE1) exceeds the cutoff values established in regulatory guidance. A Simcyp minimal physiologically based pharmacokinetic (PBPK) with advanced dissolution, absorption, and metabolism absorption model for pemigatinib was developed and validated using observed clinical pharmacokinetic (PK) data and itraconazole/rifampin drug–drug interaction (DDI) data. The model accurately predicted itraconazole DDI (approximate 90% area under the plasma drug concentration–time curve [AUC] and approximate 20% maximum plasma drug concentration [Cmax] increase). The model underpredicted rifampin induction by 100% (approximate 6.7‐fold decrease in AUC and approximate 2.6‐fold decrease in Cmax in the DDI study), presumably reflecting non‐CYP3A4 mechanisms being impacted. The verified PBPK model was then used to predict the effect of other CYP3A4 inhibitors/inducers on pemigatinib PK and pemigatinib as an inhibitor of P‐gp or OCT2/MATE1 substrates. The worst‐case scenario DDI simulation for pemigatinib as an inhibitor of P‐gp or OCT2/MATE1 substrates showed only a modest DDI effect. The recommendation based on this simulation and clinical data is to reduce pemigatinib dose for coadministration with strong and moderate CYP3A4 inhibitors. No dose adjustment is required for weak CYP3A4 inhibitors. The coadministration of strong and moderate CYP3A4 inducers with pemigatinib should be avoided. PBPK modeling suggested no dose adjustment with P‐gp or OCT2/MATE1 substrates.
How preservice and in‐service elementary teachers engage student avatars in scientific argumentation within a simulated classroom environment
Authors: Mikeska Jamie N. , Lottero‐Perdue Pamela S. 
Published: May 2022

AbstractEngaging students in scientific argumentation is a hallmark of high‐quality science instruction. Despite the importance of this practice, it is not a ubiquitous one within K‐12 classrooms since scientific argumentation is complex and difficult to learn how to do well. In this study, we examined similarities and differences in how preservice teachers (PSTs) and in‐service teachers (ISTs) facilitate an argumentation‐focused discussion with five upper elementary student avatars in an online, simulated classroom. Developing a better understanding of how science teachers at different stages of their career foster scientific argumentation will support teacher educators and researchers in designing more directed interventions to scaffold teacher learning of this complex practice. Findings showed that most teachers provided opportunities for students to engage in both argument construction and critique during these discussions. In addition, both PSTs and ISTs frequently prompted students to reference data or observations to engage in argument construction and were most likely to prompt students to agree or disagree and explain the reason for their agreement or disagreement to engage in argument critique. Finally, findings showed that ISTs used a wider variety of talk moves and used them more frequently in an integrated fashion throughout the discussions to engage the students in scientific argumentation. Implications for studying and promoting teacher learning of this complex teaching practice and for integrating simulated classrooms as practice‐based tools in science teacher education and professional development settings are discussed.