bluuebunny/crossref_metadata_2025_split huggingface dataset:
Musculoskeletal ultrasound: a useful tool for diagnosis of hip developmental dysplasia
Authors: Mureşan Simona , Mărginean Maria Oana , Voidăzan Septimiu , Vlasa Ionuţ , Sîntean Ioana 
Published: January 2019

Abstract
Developmental dysplasia of the hip (DDH) is one of the most common congenital abnormalities of the musculoskeletal apparatus in newborns. The aim of this study was to analyze the contribution of ultrasonography in the detection of DDH in newborns and infants, identifying the regional incidence of this pathology in the central area of Romania, emphasizing the risk factors that underlie DDH etiopathogenicity.
This article represents a retrospective study of 847 newborns and infants examined in the Imagistic Department of a medical center from the central area of Romania, between January 1 and December 31, 2016. The ultrasound examinations were performed for the bilateral coxofemoral joints, using the method and technique described by Graf. For subjects born in the same medical center, data regarding mother's age, birth weights, and type of delivery (natural vs. caesarian section) were statistically analyzed.
In our study group, the frequency of ultrasound diagnosis obtained from the examinations of right and left hips showed that the most frequent stage was type IA, and the rarest stage was III. The IA stage of right coxofemoral joints (87.3%) was higher than in the left coxofemoral joints (87.2%). The incidence of hip dysplasia (type III) diagnosed with ultrasound examinations in subjects from the central area of Romania was 0.2% (0.1% in both hips and 0.1% for the left coxofemoral joint).
The musculoskeletal ultrasound examination is effective in early detection of hip dysplasia. The implementation of national and regional programs that promote indications, risk factors, and the screening age for DDH in both rural and urban areas could be a step forward in the early diagnosis of hip dysplasia for newborns and infants. The low incidence of DDH from our study group is not able to identify the role of advanced age of the mother, high birth weight of the newborn, or caesarean section as risk factors involved in the etiology of hip dysplasia. The implementation of national and regional programs that promote the musculoskeletal ultrasound as a screening imagistic investigation for DDH, in both rural and urban areas, could be a step forward in the early diagnosis of hip dysplasia for newborns and infants.
A Comparison of Endoscopic Reduction for Medial Blowout Fractures Using a Bioresorbable Panel and Silastic Sheet
Authors: Kim Joo Yeon , Jung Tae Young , Kwon Jae Hwan 
Published: January 2019

Background:
The aim of the study was to compare the effectiveness of endoscopic endonasal reduction using a bioresorbable panel and silastic sheet packed with Merocel for blowout fractures of the medial orbital wall.

Design:
Retrospective study.

Methods:
The study group consisted of 147 patients who underwent endoscopic endonasal reduction of a blowout fracture of the medial orbital wall between January 2005 and December 2016. Fifty-seven fractures were repaired using a splint formed by a silastic sheet and Merocel (splint group), whereas 90 fractures were repaired using a bioresorbable panel for interposition (interposition group). Postoperative complications and surgical outcomes of the 2 groups were compared.

Results:
Preoperative diplopia in both groups (n = 30) was resolved except 1 in interposition group after the reduction. Enophthalmos was resolved in 10 cases in the splint group and in 6 cases in the interposition group. In postoperative CT scans, 20 of the 57 cases in the splint group exhibited under- or overcorrection, compared with 9 of the 90 cases in the interposition group (P < 0.05). There were no sinus infections or implant-related side effects in the interposition group except for implant extrusion in 4 cases, whereas 7 cases developed sinusitis in the splint group (P < 0.05).

Conclusions:
Endonasal endoscopic reduction using a bioresorbable panel may be considered as a surgical alternative for the treatment of medial orbital blowout fractures.
Right-Sided Complete Third Branchial Cleft Fistula
Authors: Yildirim Ugur , Atmaca Sinan , Koyuncu Mehmet 
Published: January 2019

Abstract
Branchial cleft anomalies occur due to insufficient closure of cavities during embryogenesis. These anomalies consist of cysts, sinuses, and fistulas, with the rarest type being fistulas. A 29-year-old male presented at the authors’ clinic with a right-sided complete third branchial cleft fistula. Fistula track excision surgery was successfully performed and no recurrence was observed in the 12-month follow-up after the surgery. While second branchial cleft fistula is the most common, third and fourth brancial cleft fistulas are extremely rare. In addition, they are usually incomplete and almost always on the left side.
From mathematical axioms to mathematical rules of proof: recent developments in proof analysis
Authors: Negri Sara , von Plato Jan 
Published: January 2019

A short text in the hand of David Hilbert, discovered in Göttingen a century after it was written, shows that Hilbert had considered adding a 24th problem to his famous list of mathematical problems of the year 1900. The problem he had in mind was to find criteria for the simplicity of proofs and to develop a general theory of methods of proof in mathematics. In this paper, it is discussed to what extent proof theory has achieved the second of these aims.
This article is part of the theme issue ‘The notion of ‘simple proof’ - Hilbert's 24th problem’.
Identification of proofs via syzygies
Authors: Malheiro António , Reis José Francisco 
Published: January 2019

In 1900, Hilbert gave a lecture at the International Congress of Mathematicians in Paris, for which he prepared 23 problems that mathematicians should solve during the twentieth century. It was found that there was a note on a 24th problem focusing on the problem of simplicity of proofs. One of the lines of research that was generated from this problem was the identification of proofs. In this article, we present a possible method for exploring the identification of proofs based on the membership problem original from the theory of polynomial rings. To show this, we start by giving a complete worked-out example of a membership problem, that is the problem of checking if a given polynomial belongs to an ideal generated by finitely many polynomials. This problem can be solved by considering Gröbner bases and the corresponding reductions. Each reduction is a simplification of the polynomial and it corresponds to a rewriting step. In proving that a polynomial is a member of an ideal, a rewriting process is used, and many different such processes can be considered. To better illustrate this, we consider a graph where each rewriting step corresponds to an edge, and thus a path corresponds to a rewriting process. In this paper, we consider the identification of paths, within the context of the membership problem, to propose a criterion of identification of proofs.
This article is part of the theme issue ‘The notion of ‘simple proof’ - Hilbert's 24th problem’.
A genome-wide association study identifies that the GDF5 and COL27A1 genes are associated with knee pain in UK Biobank (N = 171, 516)
Authors: Meng Weihua , Adams Mark J , Palmer Colin NA ,   The 23andMe Research Team, Shi Jingchunzi , Auton Adam , Ryan Kathleen A. , Jordan Joanne M. , Mitchell Braxton D. , Jackson Rebecca D. , Yau Michelle S. , McIntosh Andrew M , Smith Blair H 
Published: January 2019

SUMMARYObjectiveKnee pain is one of the most common musculoskeletal complaints that brings people to medical attention. We sought to identify the genetic variants associated with knee pain in 171,516 subjects from the UK Biobank cohort and replicate them using cohorts from 23andMe, the Osteoarthritis Initiative (OAI), and the Johnston County Osteoarthritis Study (JoCo).MethodsWe performed a genome-wide association study of knee pain in the UK Biobank, where knee pain was ascertained through self-report and defined as “knee pain in the last month interfering with usual activities”. A total of 22,204 cases and 149,312 controls were included in the discovery analysis. We tested our top and independent SNPs (P < 5 × 10−8) for replication in 23andMe, OAI, and JoCo, then performed a joint meta-analysis between discovery and replication cohorts using GWAMA. We calculated the narrow-sense heritability of knee pain using Genome-wide Complex Trait Analysis (GCTA).ResultsWe identified 2 loci that reached genome-wide significance, rs143384 located in the GDF5 (P = 1.32 × 10−12), a gene previously implicated in osteoarthritis, and rs2808772, located near COL27A1 (P = 1.49 × 10−8). These findings were subsequently replicated in independent cohorts and increased in significance in the joint meta-analysis (rs143384: P = 4.64 × 10−18; rs2808772: P −11 = 2.56 × 10−1’). The narrow sense heritability of knee pain was 0.08.ConclusionIn this first reported genome-wide association meta-analysis of knee pain, we identified and replicated two loci in or near GDF5 and COL27A1 that are associated with knee pain.
Expected Genotype Quality and Diploidized Marker Data from Genotyping-by-Sequencing of Urochloa spp. Tetraploids
Authors: Matias Filipe Inácio , Xavier Meireles Karem Guimarães , Nagamatsu Sheila Tiemi , Lima Barrios Sanzio Carvalho , do Valle Cacilda Borges , Carazzolle Marcelo Falsarella , Fritsche-Neto Roberto , Endelman Jeffrey B 
Published: January 2019

ABSTRACTAlthough genotyping-by-sequencing (GBS) is a well-established marker technology in diploids, the development of best practices for tetraploid species is a topic of current research. We determined the theoretical relationship between read depth and expected genotype quality (EGQ) for tetraploid vs. diploidized genotype calls. If the GBS method has 1% error, then 17 reads are needed to classify tetraploid samples as heterozygous vs. homozygous with 95% accuracy, compared with 63 reads to determine allele dosage. We developed an R script to convert tetraploid GBS data in Variant Call Format (VCF) into diploidized genotype calls and applied it to 267 interspecific hybrids of the tetraploid forage grass Urochloa (syn. Brachiaria). When reads were aligned to a mock reference genome created from GBS data of the U. brizantha cultivar ‘Marandu’, 25,678 bi-allelic SNPs were discovered, compared to approximately 3000 SNPs when aligning to the closest true reference genomes, Setaria viridis and S. italica. Crossvalidation revealed that missing genotypes were imputed by the Random Forest method with a median accuracy of 0.85, regardless of heterozygote frequency. Using the Urochloa spp. hybrids, we illustrated how filtering samples based only on GQ creates genotype bias; a depth threshold with corresponding EGQ equal to the GQ threshold is also needed, regardless of whether genotypes are called using a diploidized or allele dosage model.
Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2 islands in euchromatin
Authors: Lee Yuh Chwen G. , Ogiyama Yuki , Martins Nuno M. C. , Beliveau Brian J. , Acevedo David , Wu C.-ting , Cavalli Giacomo , Karpen Gary H. 
Published: January 2019

AbstractMembraneless pericentromeric heterochromatin (PCH) domains play vital roles in chromosome dynamics and genome stability. However, our current understanding of 3D genome organization does not include PCH domains because of technical challenges associated with repetitive sequences enriched in PCH genomic regions. We investigated the 3D architecture ofDrosophila melanogasterPCH domains and their spatial associations with euchromatic genome by developing a novel analysis method that incorporates genome-wide Hi-C reads originating from PCH DNA. Combined with cytogenetic analysis, we reveal a hierarchical organization of the PCH domains into distinct “territories.” Strikingly, H3K9me2/3-enriched regions embedded in the euchromatic genome show prevalent 3D interactions with the PCH domain. These spatial contacts require H3K9me2/3 enrichment, are likely mediated by liquid-liquid phase separation, and may influence organismal fitness. Our findings have important implications for how PCH architecture influences the function and evolution of both repetitive heterochromatin and the gene-rich euchromatin.Author summaryThe three dimensional (3D) organization of genomes in cell nuclei can influence a wide variety of genome functions. However, most of our understanding of this critical architecture has been limited to the gene-rich euchromatin, and largely ignores the gene-poor and repeat-rich pericentromeric heterochromatin, or PCH. PCH comprises large part of most eukaryotic genomes, forms 3D PCH domains in nuclei, and plays vital role in chromosome dynamics and genome stability. In this study, we developed a new method that overcomes the technical challenges imposed by the highly repetitive PCH DNA, and generated a comprehensive picture of its 3D organization. Combined with image analyses, we revealed a hierarchical organization of the PCH domains. Surprisingly, we showed that distant euchromatic regions enriched for repressive epigenetic marks also dynamically interact with the main PCH domains. These 3D interactions are mediated by liquid-liquid phase separation mechanisms, similar to how oil and vinegar separate in salad dressing, and can influence the fitness of individuals. Our discoveries have strong implications for how seemingly “junk” DNA could impact functions in the gene-rich euchromatin.
Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations
Authors: Ruiz-Cordero Roberto , Ma Junsheng , Khanna Abha , Lyons Genevieve , Rinsurongkawong Waree , Bassett Roland , Guo Ming , Routbort Mark J. , Zhang Jianjun , Skoulidis Ferdinandos , Heymach John , Roarty Emily B. , Tang Zhenya , Medeiros L. Jeffrey , Patel Keyur P. , Luthra Rajyalakshmi , Chowdhuri Sinchita Roy 
Published: January 2019

AbstractIntroductionGene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification.MethodsMutational status of EGFR, KRAS, and TP53 was used to define six mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma.ResultsThe proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with comutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival.ConclusionsThe mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into six subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.
Intrinsic spine dynamics are critical for recurrent network learning in models with and without autism spectrum disorder
Authors: Humble James , Hiratsuka Kazuhiro , Kasai Haruo , Toyoizum Taro 
Published: January 2019

AbstractIt is often assumed that Hebbian synaptic plasticity forms a cell assembly, a mutually interacting group of neurons that encodes memory. However, in recurrently connected networks with pure Hebbian plasticity, cell assemblies typically diverge or fade under ongoing changes of synaptic strength. Previously assumed mechanisms that stabilize cell assemblies do not robustly reproduce the experimentally reported unimodal and long-tailed distribution of synaptic strengths. Here, we show that augmenting Hebbian plasticity with experimentally observed intrinsic spine dynamics can stabilize cell assemblies and reproduce the distribution of synaptic strengths. Moreover, we posit that strong intrinsic spine dynamics impair learning performance. Our theory explains how excessively strong spine dynamics, experimentally observed in several animal models of autism spectrum disorder, impair learning associations in the brain.
Tad pili play a dynamic role in Caulobacter crescentus surface colonization
Authors: Sangermani Matteo , Hug Isabelle , Sauter Nora , Pfohl Thomas , Jenal Urs 
Published: January 2019

ABSTRACTBacterial surface attachment is mediated by rotary flagella and filamentous appendages called pili. Here, we describe the role of Tad pili during surface colonization of Caulobacter crescentus. Using an optical trap and microfluidic controlled flow conditions as a mimic of natural environments, we demonstrate that Tad pili undergo repeated cycles of extension and retraction. Within seconds after establishing surface contact, pili reorient cells into an upright position promoting walking-like movements against the medium flow. Pili-mediated positioning of the flagellated pole close to the surface facilitates motor-mediated mechanical sensing and promotes anchoring of the holdfast, an adhesive substance that affords long-term attachment. We present evidence that the second messenger c-di-GMP regulates pili dynamics during surface encounter in distinct ways, promoting increased activity at intermediate levels and retraction of pili at peak concentrations. We propose a model, in which flagellum and Tad pili functionally interact and together impose a ratchet-like mechanism that progressively drives C. crescentus cells towards permanent surface attachment.
Targeted sequencing of candidate genes of dyslipidemia in Punjabi Sikhs: Population-specific rare variants inGCKRpromote ectopic fat deposition
Authors: Sanghera Dharambir K. , Hopkins Ruth , Malone-Perez Megan W. , Bejar Cynthia , Tan Chengcheng , Mussa Huda , Whitby Paul , Rao Chinthapally V. , Fung KarMing A. , Lightfoot Stan , Frazer J Kimble 
Published: January 2019

AbstractDyslipidemia is a well-established risk factor for cardiovascular diseases. Although, advances in genome-wide technologies have enabled the discovery of hundreds of genes associated with blood lipid phenotypes, most of the heritability remains unexplained. Here we performed targeted resequencing of 13 bona fide candidate genes of dyslipidemia to identify the underlying biological functions. We sequenced 940 Sikh subjects with extreme serum levels of hypertriglyceridemia (HTG) and 2,355 subjects were used for replication studies; all 3,295 participants were part of the Asian Indians Diabetic Heart Study. Gene-centric analysis revealed a burden of variants for increasing HTG risk inGCKR(p=2.1×10−5),LPL(p=1.6×10−3) andMLXIPL(p=1.6×10−2) genes. Of these, three missense and damaging variants withinGCKRwere further examined for functional consequencesin vivousing a transgenic zebrafish model. All three mutations were South Asian population-specific and were largely absent in other multiethnic populations of the Exome Aggregation Consortium. We built different transgenic models of humanGCKRwith and without mutations and analyzed the effects of dietary changesin vivo. Despite the short-term feeding, profound phenotypic changes were apparent in hepatocyte histology and fat deposition associated with increased expression of GCKR in response to a high fat diet (HFD). Liver histology of theGCKRmutshowed severe fatty metamorphosis which correlated with ~7 fold increase in the mRNA expression in theGCKRmutfish even in the absence of a high fat diet. These findings suggest that functionally disruptiveGCKRvariants not only increase the risk of HTG but may enhance ectopic lipid/fat storage defects in the absence of obesity and HFD. To our knowledge, this is the first transgenic zebrafish model of a putative human disease gene built to accurately assess the influence of rare genetic changes and their phenotypic consequencesin vivo.
Viral delivery of tissue nonspecific alkaline phosphatase diminishes craniosynostosis in one of two FGFR2C342Y/+ mouse models of Crouzon syndrome
Authors: Nam Hwa Kyung , Vesela Iva , Schutte Sara Dean , Hatch Nan E. 
Published: January 2019

AbstractCraniosynostosis is the premature fusion of cranial bones. The goal of this study was to determine if delivery of recombinant tissue nonspecific alkaline phosphatase (TNAP) could prevent or diminish the severity of craniosynostosis in a C57BL/6 FGFR2C342Y/+ model of neonatal onset craniosynostosis or a BALB/c FGFR2C342Y/+ model of postnatal onset craniosynostosis. Mice were injected with a lentivirus encoding a mineral targeted form of TNAP immediately after birth. Cranial bone fusion as well as cranial bone volume, mineral content and density were assessed by micro computed tomography. Craniofacial shape was measured with calipers. Alkaline phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST) activity levels were measured in serum. Neonatal delivery of TNAP diminished craniosynostosis severity from 94% suture obliteration in vehicle treated mice to 67% suture obliteration in treated mice, p<0.02) and the incidence of malocclusion from 82.4% to 34.7% (p<0.03), with no effect on cranial bone in C57BL/6 FGFR2C342Y/+ mice. In contrast, treatment with TNAP improved cranial bone volume (p< 0.01), density (p< 0.01) and mineral content (p< 0.01) but had no effect on craniosynostosis or malocclusion in BALB/c FGFR2C342Y/+ mice. These results indicate that perinatal recombinant TNAP enzyme therapy diminishes craniosynostosis severity in the C57BL/6 FGFR2C342Y/+ neonatal onset mouse model of Crouzon syndrome, and that effects of exogenous TNAP are genetic background dependent.