bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining pathogenicity of NOTCH2 variants for diagnosis of Alagille syndrome type 2 using a large cohort of patients
Authors: Li Zhong‐Die , Abuduxikuer Kuerbanjiang , Wang Li , Hao Chen‐Zhi , Zhang Jing , Wang Meng‐Xuan , Li Li‐Ting , Qiu Yi‐Ling , Xie Xin‐Bao , Lu Yi , Wang Jian‐She 
Published: May 2022

AbstractBackground and AimsAlagille syndrome (ALGS) type 2 caused by mutations in NOTCH2 has genotypic and phenotypic heterogeneity. Diagnosis in some atypical patients with isolated hepatic presentation could be missed.MethodsUsing 2087 patients with paediatric liver manifestations, NOTCH2 allele frequencies, in‐silico prediction, protein domains and clinical features were analysed to define the pathogenicity of NOTCH2 variants for diagnosis of ALGS type 2.ResultsAmong 2087 patients with paediatric liver manifestations, significantly more NOTCH2 variants were absent in gnomAD in patients with elevated γ‐glutamyltransferase (GGT) (p = .041). Significantly more NOTCH2 variants which were absent in gnomAD were located in protein functional domains (p = .038). When missense variants were absent in gnomAD and predicted to be pathogenic by at least three out of seven in‐silico tools, they were found to be significantly associated with liver manifestations with elevated GGT (p = .003). Comparing this to patients with likely benign (LB) variants, the patients with likely‐pathogenic (LP) variants have significantly more liver manifestations with elevated GGT (p = .0001). Significantly more patients with LP variants had extra‐hepatic phenotypes of ALGS compared with those patients with LB variants (p = .0004).ConclusionWhen NOTCH2 variants are absent in gnomAD, null variants and missense variants which were predicted to be pathogenic by at least three in‐silico tools could be considered pathogenic in patients with high GGT chronic liver diseases.
FIB‐4 and incident severe liver outcomes in patients with undiagnosed chronic liver disease: A Fine‐Gray competing risk analysis
Authors: Schreiner Andrew D. , Zhang Jingwen , Moran William P. , Koch David G. , Marsden Justin , Livingston Sherry , Mauldin Patrick D. , Gebregziabher Mulugeta 
Published: May 2022

AbstractBackground and AimsThe Fibrosis‐4 index (FIB‐4) can reliably assess fibrosis risk in patients with chronic liver disease, and advanced fibrosis is associated with severe liver disease (SLD) outcomes. However, CLD is underdiagnosed in primary care. We examined the association between FIB‐4 risk strata and the incidence of SLD preceding a CLD diagnosis while considering incident CLD diagnoses as competing risks.MethodsUsing primary care clinic data between 2007 and 2018, we identified patients with two FIB‐4 scores and no liver disease diagnoses preceding the index FIB‐4. Patients were followed from index FIB‐4 until an incident SLD (a composite of cirrhosis, hepatocellular carcinoma or liver transplantation), CLD or were censored. Hazard ratios were computed using a Fine‐Gray competing risk model.ResultsOf 20 556 patients, there were 54.8% in the low, 34.8% in the indeterminate, 6.6% in the high and 3.8% in the persistently high‐risk FIB‐4 strata. During a mean 8.2 years of follow‐up, 837 (4.1%) patients experienced an SLD outcome and 11.5% of the sample received a CLD diagnosis. Of patients with an SLD event, 49% received no preceding CLD diagnosis. In the adjusted Fine‐Gray model, the indeterminate (HR 1.41, 95% CI 1.17–1.71), high (HR 4.65, 95% CI 3.76–5.76) and persistently high‐risk (HR 7.60, 95% CI 6.04–9.57) FIB‐4 risk strata were associated with a higher incidence of SLD compared to the low‐risk stratum.ConclusionsFIB‐4 scores with indeterminate‐ and high‐risk values are associated with an increased incidence of SLD in primary care patients without known CLD.
Consistent time‐homogeneous modeling of SPX and VIX derivatives
Authors: Papanicolaou Andrew 
Published: May 2022

AbstractThis paper shows how to recover a stochastic volatility model (SVM) from a market model of the VIX futures term structure. Market models have more flexibility for fitting of curves than do SVMs, and therefore are better suited for pricing VIX futures and VIX derivatives. But the VIX itself is a derivative of the S&P500 (SPX) and it is common practice to price SPX derivatives using an SVM. Therefore, consistent modeling for both SPX and VIX should involve an SVM that can be obtained by inverting the market model. This paper's main result is a method for the recovery of a stochastic volatility function by solving an inverse problem where the input is the VIX function given by a market model. Analysis will show conditions necessary for there to be a unique solution to this inverse problem. The models are consistent if the recovered volatility function is non‐negative. Examples are presented to illustrate the theory, to highlight the issue of negativity in solutions, and to show the potential for inconsistency in non‐Markov settings.
Asteroid 2008 TC3, not a polymict ureilitic but a polymict C1 chondrite parent body? Survey of 249 Almahata Sitta fragments
Authors: Bischoff Addi , Bannemann Lukas , Decker Stephan , Ebert Samuel , Haberer Siegfried , Heitmann Ursula , Horstmann Marian , Klemm Kerstin I. , Kraemer Ann‐Kathrin , Lentfort Sarah , Patzek Markus , Storz Jakob , Weyrauch Mona 
Published: May 2022

AbstractOn October 7, 2008, the asteroid 2008 TC3 exploded as it entered the Earth’s atmosphere, producing significant dust (in the atmosphere) and delivering thousands of stones in a strewn field in Sudan, collectively known as the Almahata Sitta (AhS) stones. About 600 fragments were officially recovered in 2008 and 2009. Further rocks were collected since the fall event by local people. From these stones, 249 were classified at the Institut für Planetologie in Münster (MS) known as MS‐xxx or MS‐MU‐xxx AhS subsamples. Most of these rocks are ureilitic in origin (168; 67%): 87 coarse‐grained ureilites, 60 fine‐grained ureilites, 15 ureilites with variable texture/mineralogy, four trachyandesites, and two polymict breccias. We identified 81 non‐ureilitic fragments, corresponding to 33% of the recovered samples studied in Münster. These included chondrites, namely 65 enstatite chondrites (43 EL; 22 EH), 11 ordinary chondrites (OC), one carbonaceous chondrite, and one unique R‐like chondrite. Furthermore, three samples represent a unique type of enstatite achondrite. Since all AhS stones must be regarded as individual specimens independent from each other, the number of fresh ureilite and enstatite chondrite falls in our meteorite collections has been increased by several hundred percent. Overall, the samples weigh between <1 and 250 g and have a mean mass of ~15 g. If we consider—almost 15 years after the fall—the mass calculations, observations during and after the asteroid entered the atmosphere, the mineralogy of the C1 stones AhS 91A and AhS 671, and the experimental work on fitting the asteroid spectrum (e.g., Goodrich et al., 2019; Jenniskens et al., 2010; Shaddad et al., 2010), the main portion of the meteoroid was likely made of the fine‐grained (carbonaceous) dust and was mostly lost in the atmosphere. In particular, the fact that C1 materials were found has important implications for interpreting asteroid 2008 TC3's early spectroscopic results. Goodrich et al. (2019) correctly suggested that if scientists had not recovered the “water‐free” samples (e.g., ureilites, enstatites, and OC) from the AhS strewn field, 2008 TC3 would have been assumed to be a carbonaceous chondrite meteoroid. Considering that the dominating mass of the exploding meteoroid consisted of carbonaceous materials, asteroid 2008 TC3 cannot be classified as a polymict ureilite; consequently, we state that the asteroid was a polymict carbonaceous chondrite breccia, specifically a polymict C1 object that may have formed by late accretion at least 50–100 Ma after calcium–aluminum‐rich inclusions.
Population connectivity and genetic offset in the spawning coral Acropora digitifera in Western Australia
Authors: Adam Arne A. S. , Thomas Luke , Underwood Jim , Gilmour James , Richards Zoe T. 
Published: May 2022

AbstractAnthropogenic climate change has caused widespread loss of species biodiversity and ecosystem productivity across the globe, particularly on tropical coral reefs. Predicting the future vulnerability of reef‐building corals, the foundation species of coral reef ecosystems, is crucial for cost‐effective conservation planning in the Anthropocene. In this study, we combine regional population genetic connectivity and seascape analyses to explore patterns of genetic offset (the mismatch of gene–environmental associations under future climate conditions) in Acropora digitifera across 12 degrees of latitude in Western Australia. Our data revealed a pattern of restricted gene flow and limited genetic connectivity among geographically distant reef systems. Environmental association analyses identified a suite of loci strongly associated with the regional temperature variation. These loci helped forecast future genetic offset in gradient forest and generalized dissimilarity models. These analyses predicted pronounced differences in the response of different reef systems in Western Australia to rising temperatures. Under the most optimistic future warming scenario (RCP 2.6), we predicted a general pattern of increasing genetic offset with latitude. Under the extreme climate scenario (RCP 8.5 in 2090–2100), coral populations at the Ningaloo World Heritage Area were predicted to experience a higher mismatch between current allele frequencies and those required to cope with local environmental change, compared to populations in the inshore Kimberley region. The study suggests complex and spatially heterogeneous patterns of climate‐change vulnerability in coral populations across Western Australia, reinforcing the notion that regionally tailored conservation efforts will be most effective at managing coral reef resilience into the future.
Body growth and reproductive parameters of common dolphins from the southwestern Atlantic
Authors: Grandi María Florencia , Heredia Federico M. , Sosa Drouville Ailin , Dellabianca Natalia A. , Crespo Enrique A. 
Published: May 2022

AbstractCommon dolphins, Delphinus delphis, in the southwestern Atlantic Ocean are subject to incidental mortality in fishing gear. However, no information on trends in abundance or estimates of bycatch mortality are available to evaluate the impact of this threat on the population. This study presents estimates of life history parameters using postmortem data obtained over a 17‐year period in Argentina. Ages were determined for 93 specimens, and reproductive organ samples were examined (n = 89). Immature animals ranged from 0 to 6 years in females and from 0 to 9 years in males. Mature animals ranged from 7 to 21 years in females and from 6 to 23 years in males. The asymptotic body length (L∞) described by a Gompertz model fit to age‐length data was 196 cm, 95% CI [192.45, 199.76] for females and 210.75 cm, 95% CI [206.64, 215.30] for males and was attained at 14 years in females and 15 years in males. Comparison to other populations showed that L∞ were shorter than estimates from New Zealand, similar to L∞ from eastern North Atlantic, and longer than estimates from North Pacific common dolphins. Lmax reported here were shorter than New Zealand ones but similar to those previously reported from other populations.
Resonance plays a secondary role in amplifying underwater vocalizations of Weddell seals (Leptonychotes weddellii)
Authors: Moore Jennifer L. , Terhune John M. 
Published: May 2022

AbstractDuring the breeding season, male Weddell seals (Leptonychotes weddellii) defend underwater territories using high amplitude trill vocalizations (some >190 dB re 1 μPa‐m). The source‐filter theory states that the characteristics of vocalizations are a product of both the sound produced at the source and the effects of soundwave reflection within the vocal tract. This study aimed to determine the relative influence of reflection (resonance). Weddell seal trills (tonal descending frequency sweeps ranging from >20 to <0.1 kHz) offered a unique opportunity to look for resonance in the spectral patterns, appearing as periodic peaks in amplitude over short frequency intervals. Additionally, distributions of frequencies with absolute maximum amplitude (FMA) were tested against random distributions to look for frequencies where FMAs occur more frequently than by chance. All methods exhibited evidence of resonance at 0.45–0.56 and 2.25–2.83 kHz. These frequencies would resonate in closed‐at‐both‐ends tubes with lengths of 32–40 and 6–8 cm, respectively. These lengths approximate the likely sizes of the trachea and larynx or pharynx respectively. The amplitudes of the underwater calls of Weddell seals primarily result from the amplitude generated by the sound source in the larynx with some additional amplitude associated with resonance in the vocal tract.
Alternative splicing as a key player in the fine‐tuning of the immunity response in Arabidopsis
Authors: Kufel Joanna , Diachenko Nataliia , Golisz Anna 
Published: May 2022

AbstractPlants, like animals, are constantly exposed to abiotic and biotic stresses, which often inhibit plant growth and development, and cause tissue damage, disease, and even plant death. Efficient and timely response to stress requires appropriate co‐ and posttranscriptional reprogramming of gene expression. Alternative pre‐mRNA splicing provides an important layer of this regulation by controlling the level of factors involved in stress response and generating additional protein isoforms with specific features. Recent high‐throughput studies have revealed that several defence genes undergo alternative splicing that is often affected by pathogen infection. Despite extensive work, the exact mechanisms underlying these relationships are still unclear, but the contribution of alternative protein isoforms to the defence response and the role of regulatory factors, including components of the splicing machinery, have been established. Modulation of gene expression in response to stress includes alternative splicing, chromatin remodelling, histone modifications, and nucleosome occupancy. How these processes affect plant immunity is mostly unknown, but these facets open new regulatory possibilities. Here we provide an overview of the current state of knowledge and recent findings regarding the growing importance of alternative splicing in plant response to biotic stress.
Genomic prediction in doubled haploid maize (Zea mays) populations under water stress at flowering and well‐watered conditions using high‐density single‐nucleotide polymorphisms
Authors: B. V. Ananda Kumar , S. R. Venkatachalam , R. Ravikesavan , R. Narasimhulu , P. Kathirvelan , Selvarangam Venkatesh , Pandravada Anand , Srivastava Ashish , D. C. Balasundara , Babu Raman , Das Sayan 
Published: May 2022

AbstractThe most important applications of genomic selection (GS) in maize breeding is to predict and identify the best untested lines from biparental populations, when the training and validation sets are derived from the same cross. A total of 300 hybrids were generated using doubled haploid lines crossed to single known tester. The test hybrids and checks were evaluated for drought tolerance, grain yield and yield attributes under well‐watered (WW) and water stress at flowering (WSF) conditions during rabi 2018 at Hyderabad and Aurangabad locations. The study was further deep dived and practiced GS using 3352 single‐nucleotide polymorphism (SNP) markers. An extension of the genomic best linear unbiassed predictor that incorporates genotype × environment (GE) interaction was used to predict genotypic values; cross‐validation methods were applied to quantify prediction accuracy. Our results showed that the highest cross‐validation prediction accuracy for grain yield was 0.47 under WSF condition in TPS3, whereas under WW condition, prediction accuracy was 0.44 in TPS2, which is statistically on par with WSF condition. Among the secondary traits, the peak GS accuracies recorded for the traits anthesis silking interval (0.52) and ears per plant (0.48) under WSF. Under both the water regimes, anthesis silking interval and plant height recorded higher prediction accuracy when compared with grain yield. Hence, GS could be practiced for anthesis silking interval and ears per plant under stress condition in maize. Further while optimizing the population size, it was revealed from the study that increasing size of the population increases GS accuracy and TPS2 considered as optimum size of population for GS prediction.
Clinical profiles of post‐infectious arthritis and transient synovitis of the hip in children
Authors: Ananthanathorn Paween , Sukharomana Maynart , Charuvanij Sirirat 
Published: May 2022

AbstractBackgroundAcute inflammatory arthritides can present as a result of immune reaction following infections. Post‐infectious arthritis and transient synovitis of the hip in children are included in this disease entity. The aim of this study was to describe the clinical profiles of post‐infectious arthritis and transient synovitis of the hip in Thai children.MethodsA retrospective review was performed at a tertiary care hospital in Bangkok, Thailand from January 2005 to July 2017.ResultsEighty‐six patients (56 boys and 30 girls) were included in this study. Mean age was 8.4 ± 4.8 years. Reactive arthritis was diagnosed in two patients (2.3%) following Salmonella spp. and Chlamydia trachomatis infections. Post‐streptococcal reactive arthritis was present in 10 patients (11.6%). Transient synovitis of the hip was found in 30 patients (34.9%). Forty‐four patients (51.2%) were clinically diagnosed with post‐infectious arthritis. Mono/oligoarthritis was the most common clinical profile (84.9%). The distribution of lower‐extremity involvement was as follows: hip, 47.6%; knee, 46.5%; and ankle joints, 30.2%. The documented preceding illness consisted mostly of upper respiratory tract symptoms (30.2%). Non‐steroidal anti‐inflammatory drugs were prescribed for 70 patients (81.4%).ConclusionMono/oligoarthritis of the lower extremity was the main clinical profile. Preceding viral illness was documented in one‐third of children. Reactive arthritis was rarely seen.
Locating facilities under competition and market expansion: Formulation, optimization, and implications
Authors: Lin Yun Hui , Tian Qingyun , Zhao Yanlu 
Published: May 2022

As the ongoing battle between brick‐and‐mortar stores and e‐commerce shops escalates, managers of the former are becoming more cautious regarding their strategic store site selection and decoration decisions, particularly if foreseeable competition from rival companies exists. This paper investigates a bilevel competitive facility location (BCFL) problem, where two companies, a leader and a follower, plan to enter a market sequentially. Each company has a budget to open and design facilities. The goal is to maximize expected revenue that is forecasted through a discrete choice model. To reflect a practical environment, we further consider a situation with elastic demand, explaining the market expansion effect when customers are offered better service due to the opening of new facilities. We formulate the problem as a nonlinear 0‐1 bilevel program. Because of the bilevel structure and the market expansion effect, this problem is so challenging that we are unaware of any exact algorithms in the literature. Motivated by this gap, we develop an exact framework that leverages the state‐of‐the‐art value‐function–based approach. However, this framework requires solving a mixed‐integer nonconvex optimization problem (MINOP) at each iteration, which is computationally prohibitive even for medium‐scale instances. To mitigate the intractability, we propose a new framework that avoids MINOP and tackles instances with hundreds of location variables. Finally, we conduct extensive computational studies to show the efficiency and effectiveness of our method as well as provide insightful guidance for managers to have win–win/dominate outcomes and choose an appropriate market size function when dealing with expansion decisions in chained business operations.
Does governance ease the overhead squeeze experienced by nonprofits?
Authors: Parsa Iman , Eftekhar Mahyar , Corbett Charles J 
Published: May 2022

Nonprofits' performance is often evaluated based, in part, on their program spending ratio (PSR). Yet, ranking nonprofits based on PSR has been criticized because it is an imprecise index of a nonprofit's actual social impact. Further, too much emphasis on PSR creates an incentive for nonprofits to increase their program spending at the expense of investing in overhead, regardless of the social value it generates. In extreme cases, excessive focus on PSR can create incentives to manipulate or even misreport financial statements. Communicating information regarding governance can potentially counterbalance the pressures created by this focus on PSR. In 2008, the U.S. Internal Revenue Service implemented significant changes in the type of information that nonprofits are required to disclose, which helps them to better display their governance quality. Studying the tax forms of 38,226 nonprofits active in social services and relief operations during 2010–2017, we find that governance quality is now an important factor in driving public donations to nonprofits, although PSR still remains a key driver. Moreover, our findings show that better governance is associated with a lower likelihood of misreporting, consistent with the argument that better governance reduces the pressure to report a high PSR. Overall, our results suggest that nonprofits should consider improving their governance quality in their strategies for securing donation income, even though that may lead to lower PSR levels.
Antidepressant‐induced serotonin syndrome in older patients: a cross‐sectional study
Authors: Erken Neziha , Kaya Derya , Dost Fatma Sena , Ates Bulut Esra , Isik Ahmet Turan 
Published: May 2022

AbstractBackgroundWidespread prescription of antidepressants and their resulting role in serotonin syndrome (SS) are of great importance for clinical practice in the elderly. This study aims to investigate possible associations of antidepressant drug‐induced SS with related variables in these patients.MethodsA total of 238 older adults using antidepressants were included. Patients who fulfilled the Hunter Serotonin Toxicity Criteria (HSTC) for SS were considered as the clinical groups (mild, moderate, or severe), and those who did not as the control group. We recorded all patients' demographic and clinical characteristics, including age, gender, comorbidity index, number of medications, daily equivalent dose of the relevant antidepressant according to fluoxetine per day, electrocardiogram test results, laboratory results, and management.ResultsThe mean age of all patients was 75.4 ± 7.6 years and 63.4% were female. Sixty patients had SS, while 178 patients did not. There was a significant difference between those with and without SS in terms of gender, frequency of combination antidepressant therapy, and daily equivalent antidepressant dose (P < 0.05). The most common diagnostic findings in SS patients were tremor and hyperreflexia and 31.7% was mild, and moderate in 68.3% with higher median age and number of medications (P < 0.041). Antidepressants were discontinued in all patients regardless of severity, of whom 71.7% were treated with benzodiazepines and 36.7% with cyproheptadine. After adjusting for age and sex, association with use of SSRI + SNRI, use of any combination therapy, and daily equivalent dose remained significant.ConclusionsThe widespread single or combined use of antidepressants in older adults represents an increased clinical concern for SS and physicians should be aware of this drug‐related complication in older patients.