bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of a mouse model of the neurodevelopmental disorder with dysmorphic facies and distal limb anomalies syndrome
Authors: Zapata Gerardo , Yan Keqin , Picketts David J 
Published: May 2022

Abstract
Heterozygous variants in bromodomain and plant homeodomain containing transcription factor (BPTF) cause the neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) syndrome (MIM#617755) characterized by intellectual disability, speech delay and postnatal microcephaly. BPTF functions within nucleosome and remodeling factor (NURF), a complex comprising sucrose non-fermenting like (SNF2L), an Imitation SWItching (ISWI) chromatin remodeling protein encoded by the SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1 (SMARCA1) gene. Surprisingly, ablation of Smarca1 resulted in mice with enlarged brains, a direct contrast to the phenotype of NEDDFL patients. To model the NEDDFL syndrome, we generated forebrain-specific Bptf knockout (Bptf conditional Knockout (cKO)) mice. The Bptf cKO mice were born in normal Mendelian ratios, survived to adulthood but were smaller in size with severe cortical hypoplasia. Prolonged progenitor cell cycle length and a high incidence of cell death reduced the neuronal output. Cortical lamination was also disrupted with reduced proportions of deep layer neurons, and neuronal maturation defects that impaired the acquisition of distinct cell fates (e.g. COUP-TF-interacting protein 2 (Ctip2)+ neurons). RNAseq and pathway analysis identified altered expression of fate-determining transcription factors and the biological pathways involved in neural development, apoptotic signaling and amino acid biosynthesis. Dysregulated genes were enriched for MYC Proto-Oncogene, BHLH Transcription Factor (Myc)-binding sites, a known BPTF transcriptional cofactor. We propose the Bptf cKO mouse as a valuable model for further study of the NEDDFL syndrome.
Molecular Network Analyses Implicate Death-Associated Protein Kinase 3 (DAPK3) as a Key Factor in Colitis-Associated Dysplasia Progression
Authors: Chen Huey-Miin , MacDonald Justin A 
Published: May 2022

Abstract

Background
Ulcerative colitis (UC) is a progressive disorder that elevates the risk of colon cancer development through a colitis-dysplasia-carcinoma sequence. Gene expression profiling of colitis-associated lesions obtained from patients with varied extents of UC can be mined to define molecular panels associated with colon cancer development.

Methods
Differential gene expression profiles of 3 UC clinical subtypes and healthy controls were developed for the GSE47908 microarray data set of healthy controls, left-sided colitis, pancolitis, and colitis-associated dysplasia (CAD) using limma R.

Results
A gene ontology enrichment analysis of differentially expressed genes (DEGs) revealed a shift in the transcriptome landscape as UC progressed from left-sided colitis to pancolitis to CAD, from being immune-centric to being cytoskeleton-dependent. Hippo signaling (via Yes-associated protein [YAP]) and Ephrin receptor signaling were the top canonical pathways progressively altered in concert with the pathogenic progression of UC. A molecular interaction network analysis of DEGs in left-sided colitis, pancolitis, and CAD revealed 1 pairwise line, or edge, that was topologically important to the network structure. This edge was found to be highly enriched in actin-based processes, and death-associated protein kinase 3 (DAPK3) was a critical member and sole protein kinase member of this network. Death-associated protein kinase 3 is a regulator of actin-cytoskeleton reorganization that controls proliferation and apoptosis. Differential correlation analyses revealed a negative correlation for DAPK3-YAP in healthy controls that flipped to positive in left-sided colitis. With UC progression to CAD, the DAPK3-YAP correlation grew progressively more positive.

Conclusion
In summary, DAPK3 was identified as a candidate gene involved in UC progression to dysplasia.
Comparative Efficacy of Biologic Therapies for Inducing Response and Remission in Fistulizing Crohn’s Disease: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Authors: Shehab Mohammad , Alrashed Fatema , Heron Valérie , Restellini Sophie , Bessissow Talat 
Published: May 2022

Abstract

Background
The medical treatment of fistulizing Crohn’s disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD.

Methods
We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI).

Results
In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55).

Conclusions
Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.
Assessment of Regulatory Compliance Testing for Vitamin D in Infant Formula—Impact of Delegated Regulation (EU) 2019/828
Authors: Gilliland Donald L , Gill Brendon D , Kissling Roger C , Starkey Dustin E , Indyk Harvey E , McMahon Adrienne , Broek Arnold P , van Gool Martine P , Cruijsen Hans M M , Konings Erik J M , Campos-Gimenez Esther 
Published: May 2022

Abstract

Background
Since the publication of Standard Method Performance Requirements (SMPR®) for vitamin D in infant formula (SMPR 2011.004) by AOAC INTERNATIONAL, revised vitamin D limits have been recommended by the European Food Safety Authority (EFSA) for infant formula and adopted in Commission Delegated Regulation (EU) 2019/828. The vitamin D range introduced, 2–2.5 μg/100 kcal, is significantly narrower than previous limits specified by Codex Standard 72–1981 and requires lower method reproducibility metrics to adequately assess regulatory compliance. The narrower limits for vitamin D present a significant challenge for current-generation reference analytical methods that comply with SMPR 2011.004.

Objective
We evaluate the impact of Delegated Regulation (EU) 2019/828 on the demonstrated performance of AOAC Method 2016.05/ISO 20636:2018 to assess the likelihood that vitamin D results produced by the method would be found outside the EU limits when testing infant formula that is compliant as manufactured.

Methods
AOAC Method 2016.05/ISO 20636:2018, specifically data generated during multi-laboratory study, was used as a basis for statistical evaluation of the impact of the narrower EU vitamin D limits.

Results
The review of AOAC Method 2016.05/ISO 20636:2018 method performance against the vitamin D regulatory range introduced in (EU) 2019/828 indicates methods capable of performing in alignment with SMPR 2011.004 are likely to produce results that fail to meet EU requirements.

Conclusions
Our assessment illustrates the high probability that a well-manufactured product with vitamin D levels within the EU regulatory range would fail to meet the regulatory requirements due to analytical method variability when tested using fit-for-purpose methods. Further, required method performance cannot be expected with the future development of new methods. To avoid this, consideration should be given to aligning proposed regulatory limits with method performance metrics of current-generation compendial methods.

Highlights
Current, state-of-the-art methods cannot consistently verify infant formula product compliance for vitamin D in accordance with (EU) 2019/828.
Sensory attributes, dog preference ranking, and oxidation rate evaluation of sorghum-based baked treats supplemented with soluble animal proteins
Authors: Lema Almeida Krystina A , Koppel Kadri , Aldrich Charles G 
Published: May 2022

Abstract
Treats are offered to dogs to reinforce the animal–owner bond and as rewards. Wheat, which contains gluten (gliadin and glutenin proteins), is often used in treats. The United States is a leading producer of sorghum which might be an alternative; however, it does not have functional properties to form viscoelastic doughs, because it is mainly composed of kafirin protein. Therefore, the objectives of this study were to determine the effects of supplementing soluble animal proteins in whole sorghum rotary-molded baked dog treats on dog preference, sensory attributes, and oxidation rate. The treats were produced in triplicate in a 2 x 4 + 1 augmented factorial arrangement of treatments. Two whole sorghum flours (WWS and WRS), four protein sources [none (NC), spray-dried plasma (SDP), egg protein (EP), and gelatin (GL)], and a positive control with wheat (WWF-GTN) were evaluated. A preference ranking test with twelve dogs was performed. Additionally, five trained panelists scored the intensity of appearance, aroma, flavor, texture/mouthfeel, and aftertaste attributes. Finally, the treats were stored at 30 °C and 60% RH, and hexanal concentrations were measured on days 0, 28, 56, and 112. The data was analyzed using the statistical software SAS for the animal and oxidation rate evaluations with significance considered at P&lt;0.05. The descriptive sensory evaluation data was analyzed using multivariate analysis (XLSTAT). The dogs did not detect differences among WWF-GTN, WWS, or WRS treats when evaluated together. However, the WWF-GTN, WWS-SDP, and WWS-EP treatments were preferred among the white sorghum treatments. The EP treatments led to some consumption difficulties by dogs because of their hard texture. The panelists reported a high degree of variation in the appearance and texture across treatments. The WRS and WWS treats with SDP or EP were darker, while NC treats had more surface cracks. Initial crispness, hardness, and fracturability were higher in EP treatments compared to all other sorghum treatments. The predominant flavor and aftertaste identified were “grainy.” The hexanal values for all treats were &lt;1.0 mg/kg except for the EP treatments that had higher values (2.0–19.3 mg/kg) across the shelf-life test. This work indicated that the replacement of WWF-GTN by WWS and WRS, along with soluble animal proteins like SDP or GL would produce comparable preference by dogs, oxidation rates, product aromatics, flavor, aftertaste attributes, and, at a lower degree, product texture.
Non-resonant relaxation of anisotropic globular clusters
Authors: Tep Kerwann , Fouvry Jean-Baptiste , Pichon Christophe 
Published: May 2022

ABSTRACT
Globular clusters are dense stellar systems whose core slowly contracts under the effect of self-gravity. The rate of this process was recently found to be directly linked to the initial amount of velocity anisotropy: tangentially anisotropic clusters contract faster than radially anisotropic ones. Furthermore, initially anisotropic clusters are found to generically tend towards more isotropic distributions during the onset of contraction. Chandrasekhar’s ‘non-resonant’ (NR) theory of diffusion describes this relaxation as being driven by a sequence of local two-body deflections along each star’s orbit. We explicitly tailor this NR prediction to anisotropic clusters, and compare it with N-body realizations of Plummer spheres with varying degrees of anisotropy. The NR theory is shown to recover remarkably well the detailed shape of the orbital diffusion and the associated initial isotropization, up to a global multiplicative prefactor which increases with anisotropy. Strikingly, a simple effective isotropic prescription provides almost as good a fit, as long as the cluster’s anisotropy is not too strong. For these more extreme clusters, accounting for long-range resonant relaxation may be necessary to capture these clusters’ long-term evolution.
HD 28109 hosts a trio of transiting Neptunian planets including a near-resonant pair, confirmed by ASTEP from Antarctica
Authors: Dransfield Georgina , Triaud Amaury H M J , Guillot Tristan , Mekarnia Djamel , Nesvorný David , Crouzet Nicolas , Abe Lyu , Agabi Karim , Buttu Marco , Cabrera Juan , Gandolfi Davide , Günther Maximilian N , Rodler Florian , Schmider François-Xavier , Stee Philippe , Suarez Olga , Collins Karen A , Dévora-Pajares Martín , Howell Steve B , Matthews Elisabeth C , Standing Matthew R , Stassun Keivan G , Stockdale Chris , Quinn Samuel N , Ziegler Carl , Crossfield Ian J M , Lissauer Jack J , Mann Andrew W , Matson Rachel , Schlieder Joshua , Zhou George 
Published: May 2022

ABSTRACT
We report on the discovery and characterization of three planets orbiting the F8 star HD 28109, which sits comfortably in ${TESS}$’s continuous viewing zone. The two outer planets have periods of $\rm 56.0067 \pm 0.0003~d$ and $\rm 84.2597_{-0.0008}^{+0.0010}~d$, which implies a period ratio very close to that of the first-order 3:2 mean motion resonance, exciting transit timing variations (TTVs) of up to $\rm 60\, min$. These two planets were first identified by ${TESS}$, and we identified a third planet in the ${TESS}$photometry with a period of $\rm 22.8911 \pm 0.0004~d$. We confirm the planetary nature of all three planetary candidates using ground-based photometry from Hazelwood, ${ASTEP}$, and LCO, including a full detection of the $\rm \sim 9\, h$ transit of HD 28109 c from Antarctica. The radii of the three planets are ${\it R}_b=2.199_{-0.10}^{+0.098} ~{\rm R}_{\oplus }$, ${\it R}_c=4.23\pm 0.11~ {\rm R}_{\oplus }$, and ${\it R}_d=3.25\pm 0.11 ~{\rm R}_{\oplus }$; we characterize their masses using TTVs and precise radial velocities from ESPRESSO and HARPS, and find them to be ${\it M}_b=18.5_{-7.6}^{+9.1}~M_{\oplus }$, ${\it M}_c=7.9_{-3.0}^{+4.2}~{\rm M}_{\oplus }$, and ${\it M}_d=5.7_{-2.1}^{+2.7}~{\rm M}_{\oplus }$, making planet b a dense, massive planet while c and d are both underdense. We also demonstrate that the two outer planets are ripe for atmospheric characterization using transmission spectroscopy, especially given their position in the CVZ of James Webb Space Telescope. The data obtained to date are consistent with resonant (librating) and non-resonant (circulating) solutions; additional observations will show whether the pair is actually locked in resonance or just near-resonant.
Using machine learning to identify extragalactic globular cluster candidates from ground-based photometric surveys of M87
Authors: Barbisan Emilia , Huang Jeff , Dage Kristen C , Haggard Daryl , Arnason Robin , Bahramian Arash , Clarkson William I , Kundu Arunav , Zepf Stephen E 
Published: May 2022

ABSTRACT
Globular clusters (GCs) have been at the heart of many longstanding questions in many sub-fields of astronomy and, as such, systematic identification of GCs in external galaxies has immense impacts. In this study, we take advantage of M87’s well-studied GC system to implement supervised machine learning (ML) classification algorithms – specifically random forest and neural networks – to identify GCs from foreground stars and background galaxies, using ground-based photometry from the Canada–France–Hawaii Telescope (CFHT). We compare these two ML classification methods to studies of ‘human-selected’ GCs and find that the best-performing random forest model can reselect 61.2 per cent ± 8.0 per cent of GCs selected from HST data (ACSVCS) and the best-performing neural network model reselects 95.0 per cent ± 3.4 per cent. When compared to human-classified GCs and contaminants selected from CFHT data – independent of our training data – the best-performing random forest model can correctly classify 91.0 per cent ± 1.2 per cent and the best-performing neural network model can correctly classify 57.3 per cent ± 1.1 per cent. ML methods in astronomy have been receiving much interest as Vera C. Rubin Observatory prepares for first light. The observables in this study are selected to be directly comparable to early Rubin Observatory data and the prospects for running ML algorithms on the upcoming data set yields promising results.
On the numerical integration of an explicit solution of the homologous collapse’s radial evolution in time
Authors: Calvo Manuel , Elipe Antonio , Rández Luis 
Published: May 2022

ABSTRACT
In a recent paper, Slepian and Philcox derive an explicit solution of the homologous collapse from rest of a uniform density sphere under its self-gravity as a function of time. Their solution is given in terms of two curvilinear integrals along a suitable Jordan contour; in practice, it must be approximated by a quadrature rule. The aim of this paper is to examine how the choice of the contour and the quadrature rule affects the accuracy and the efficiency of this integral solution approximation. More precisely, after a study of the complex roots of a transcendental equation that relates time with the variable, some alternative Jordan contours that turn out to be more convenient are proposed. Then, by using as quadrature rule the composite trapezoidal rule because of its reliability and spectral convergence accuracy, some numerical experiments are presented to show that the combination of contours and quadrature rule allows us to obtain numerical results with high accuracy and low computational cost.
Multi-institutional study of the frequency, genomic landscape, and outcome of IDH-mutant glioma in pediatrics
Authors: Yeo Kee Kiat , Alexandrescu Sanda , Cotter Jennifer A , Vogelzang Jayne , Bhave Varun , Li Marilyn M , Ji Jianling , Benhamida Jamal K , Rosenblum Marc K , Bale Tejus A , Bouvier Nancy , Kaneva Kristiyana , Rosenberg Tom , Lim-Fat Mary Jane , Ghosh Hia , Martinez Migdalia , Aguilera Dolly , Smith Amy , Goldman Stewart , Diamond Eli L , Gavrilovic Igor , MacDonald Tobey J , Wood Matthew D , Nazemi Kellie J , Truong AiLien , Cluster Andrew , Ligon Keith L , Cole Kristina , Bi Wenya Linda , Margol Ashley S , Karajannis Matthias A , Wright Karen D 
Published: May 2022

Abstract

Background
The incidence and biology of IDH1/2 mutations in pediatric gliomas are unclear. Notably, current treatment approaches by pediatric and adult providers vary significantly. We describe the frequency and clinical outcomes of IDH1/2-mutant gliomas in pediatrics.

Methods
We performed a multi-institutional analysis of the frequency of pediatric IDH1/2-mutant gliomas, identified by next-generation sequencing (NGS). In parallel, we retrospectively reviewed pediatric IDH1/2-mutant gliomas, analyzing clinico-genomic features, treatment approaches, and outcomes.

Results
Incidence: Among 851 patients with pediatric glioma who underwent NGS, we identified 78 with IDH1/2 mutations. Among patients 0–9 and 10–21 years old, 2/378 (0.5%) and 76/473 (16.1%) had IDH1/2-mutant tumors, respectively. Frequency of IDH mutations was similar between low-grade glioma (52/570, 9.1%) and high-grade glioma (25/277, 9.0%). Four tumors were graded as intermediate histologically, with one IDH1 mutation. Outcome: Seventy-six patients with IDH1/2-mutant glioma had outcome data available. Eighty-four percent of patients with low-grade glioma (LGG) were managed observantly without additional therapy. For low-grade astrocytoma, 5-year progression-free survival (PFS) was 42.9% (95%CI:20.3–63.8) and, despite excellent short-term overall survival (OS), numerous disease-related deaths after year 10 were reported. Patients with high-grade astrocytoma had a 5-year PFS/OS of 36.8% (95%CI:8.8–66.4) and 84% (95%CI:50.1–95.6), respectively. Patients with oligodendroglioma had excellent OS.

Conclusions
A subset of pediatric gliomas is driven by IDH1/2 mutations, with a higher rate among adolescents. The majority of patients underwent upfront observant management without adjuvant therapy. Findings suggest that the natural history of pediatric IDH1/2-mutant glioma may be similar to that of adults, though additional studies are needed.
Aggregate Confusion: The Divergence of ESG Ratings
Authors: Berg Florian , Kölbel Julian F , Rigobon Roberto 
Published: May 2022

Abstract
This paper investigates the divergence of environmental, social, and governance (ESG) ratings based on data from six prominent ESG rating agencies: Kinder, Lydenberg, and Domini (KLD), Sustainalytics, Moody’s ESG (Vigeo-Eiris), S&P Global (RobecoSAM), Refinitiv (Asset4), and MSCI. We document the rating divergence and map the different methodologies onto a common taxonomy of categories. Using this taxonomy, we decompose the divergence into contributions of scope, measurement, and weight. Measurement contributes 56% of the divergence, scope 38%, and weight 6%. Further analyzing the reasons for measurement divergence, we detect a rater effect where a rater’s overall view of a firm influences the measurement of specific categories. The results call for greater attention to how the data underlying ESG ratings are generated.
A Cutaneous Transposition Inversion Flap to Treat Symptomatic Subcutaneous Trochanteric or Soft Tissue Defects After Hip Arthroplasty: A Technical Note
Authors: Liebe Jonas , Lehnen Aude , Jandali Abdul R. , Meier Christoph , Wahl Peter 
Published: May 2022

Introduction:
Up to 17% of patients with total hip arthroplasty (THA) suffer from greater trochanteric or lateral trochanteric pain. Subcutaneous soft tissue or trochanteric bone substance defects with protrusion of the underlying stem may be challenging causes.

Surgical Technique:
We present the surgical technique of a de-epithelialized cutaneous transposition inversion flap to cover subcutaneous implant protrusion, performed successfully in a patient with posttraumatic trochanteric defect following THA after failed internal fixation for a trochanteric fracture.

Results and Conclusion:
The patient had no more trochanteric pain, allowing her to walk, sit, and sleep without pain. The THA protrusion was no longer palpable under the uneventfully healed skin. The technique described is relatively simple and may help improve therapy in patients with symptomatic trochanteric bone or soft tissue defects.

Level of Evidence:
Level IV, Special technical article.