bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interstitial macrophage-derived thrombospondin-1 contributes to hypoxia-induced pulmonary hypertension
Authors: Kumar Rahul , Mickael Claudia , Kassa Biruk , Sanders Linda , Hernandez-Saavedra Daniel , Koyanagi Daniel E , Kumar Sushil , Pugliese Steve C , Thomas Stacey , McClendon Jazalle , Maloney James P , Janssen William J , Stenmark Kurt R , Tuder Rubin M , Graham Brian B 
Published: November 2019

Abstract

Aims
Transforming growth factor-β (TGF-β) signalling is required for chronic hypoxia-induced pulmonary hypertension (PH). The activation of TGF-β by thrombospondin-1 (TSP-1) contributes to the pathogenesis of hypoxia-induced PH. However, neither the cellular source of pathologic TSP-1 nor the downstream signalling pathway that link activated TGF-β to PH have been determined. In this study, we hypothesized that circulating monocytes, which are recruited to become interstitial macrophages (IMs), are the major source of TSP-1 in hypoxia-exposed mice, and TSP-1 activates TGF-β with increased Rho-kinase signalling, causing vasoconstriction.

Methods and results
Flow cytometry revealed that a specific subset of IMs is the major source of pathologic TSP-1 in hypoxia. Intravenous depletion and parabiosis experiments demonstrated that these cells are circulating prior to recruitment into the interstitium. Rho-kinase-mediated vasoconstriction was a major downstream target of active TGF-β. Thbs1 deficient bone marrow (BM) protected against hypoxic-PH by blocking TGF-β activation and Rho-kinase-mediated vasoconstriction.

Conclusion
In hypoxia-challenged mice, BM derived and circulating monocytes are recruited to become IMs which express TSP-1, resulting in TGF-β activation and Rho-kinase-mediated vasoconstriction.
Identification of Disease-associated Traits and Clonotypes in the T Cell Receptor Repertoire of Monozygotic Twins Affected by Inflammatory Bowel Diseases
Authors: Rosati Elisa , Pogorelyy Mikhail V , Dowds C Marie , Moller Frederik T , Sorensen Signe B , Lebedev Yuri B , Frey Norbert , Schreiber Stefan , Spehlmann Martina E , Andersen Vibeke , Mamedov Ilgar Z , Franke Andre 
Published: November 2019

AbstractBackground and AimsIntestinal inflammation in inflammatory bowel diseases [IBD] is thought to be T cell mediated and therefore dependent on the interaction between the T cell receptor [TCR] and human leukocyte antigen [HLA] proteins expressed on antigen presenting cells. The collection of all TCRs in one individual, known as the TCR repertoire, is characterised by enormous diversity and inter-individual variability. It was shown that healthy monozygotic [MZ] twins are more similar in their TCR repertoire than unrelated individuals. Therefore MZ twins, concordant or discordant for IBD, may be useful to identify disease-related and non-genetic factors in the TCR repertoire which could potentially be used as disease biomarkers.MethodsEmploying unique molecular barcoding that can distinguish between polymerase chain reaction [PCR] artefacts and true sequence variation, we performed deep TCRα and TCRβ repertoire profiling of the peripheral blood of 28 MZ twin pairs from Denmark and Germany, 24 of whom were discordant and four concordant for IBD.ResultsWe observed disease- and smoking-associated traits such as sharing, diversity and abundance of specific clonotypes in the TCR repertoire of IBD patients, and particularly in patients with active disease, compared with their healthy twins.ConclusionsOur findings identified TCR repertoire features specific for smokers and IBD patients, particularly when signs of disease activity were present. These findings are a first step towards the application of TCR repertoire analyses as a valuable tool to characterise inflammatory bowel diseases and to identify potential biomarkers and true disease causes.
Nitrogen Availability Decreases the Severity of Snow Storm Damage in a Temperate Forest
Authors: Walter Christopher A , Burnham Mark B , Adams Mary Beth , McNeil Brenden E , Deel Lindsay N , Peterjohn William T 
Published: November 2019

Abstract
Storms are among the greatest natural disturbances in temperate forests, and increased nitrogen (N) availability is thought to increase storm damage. However, the extent to which N availability increases damage from snowfall is less clear. To test how N availability might affect the susceptibility of trees to snow damage in a temperate forest, we took advantage of an opportunistic storm and surveyed damage in fertilized and unfertilized stands, and across a native N availability gradient. In response to a severe, early season snow storm—a consequence of Superstorm Sandy—the percentages of both basal area and stems damaged were lower in a fertilized watershed than in an unfertilized watershed. Across the native N availability gradient, the percentage of basal area damaged by snow decreased with higher soil N. The effects of N availability on damage were also affected by tree species. Our results suggest that N availability decreases damage from snow storms, contrary to our hypotheses drawn from broader studies. Understanding the relation between storm damage and N availability is important, considering the global increase in N deposition, and since severe storms are likely to become more prevalent with climate change.
Institutionalizing quality within national health systems: key ingredients for success
Authors: Kandasami Stephanie , Syed Shamsuzzoha Babar , Edward Anbrasi , Sodzi-Tettey Sodzi , Garcia-Elorrio Ezequiel , Mensah Abrampah Nana , Hansen Peter M 
Published: November 2019

AbstractQuality improvement initiatives can be fragmented and short-term, leading to missed opportunities to improve quality in a systemic and sustainable manner. An overarching national policy or strategy on quality, informed by frontline implementation, can provide direction for quality initiatives across all levels of the health system. This can strengthen service delivery along with strong leadership, resources, and infrastructure as essential building blocks for the health system. This article draws on the proceedings of an ISQua conference exploring factors for institutionalizing quality of care within national systems. Active learning, inclusive of peer-to-peer learning and exchange, mentoring and coaching, emerged as a critical success factor to creating a culture of quality. When coupled by reinforcing elements like strong partnerships and coordination across multiple levels, engagement at all health system levels and strong political commitment, this culture can be cascaded to all levels requiring policy, leadership, and the capabilities for delivering quality healthcare.
Impact of dietary vitamin D3 supplements in nursery diets on subsequent growth and bone responses of pigs during an immune challenge
Authors: McCue Morgan , Reichert Jamie L , Crenshaw Thomas D 
Published: November 2019

Abstract
Limited evidence is available to validate beneficial responses from extra nutrient supplements for mediation of growth suppression that results from immune challenges. Extrarenal roles of vitamin D metabolites in immune function implicate vitamin D3 supplements as a nutrient for potential beneficial effects. The current objective was to assess growth and bone ash responses to dietary vitamin D3 (D) supplements for growing pigs undergoing an immune challenge. At weaning, 216 crossbred pigs (4 pigs/pen, 6 pens/treatment) were randomly allotted within sex and weight blocks to 1 of the 9 treatments. Treatments included D supplements (0, 100, or 800 IU/kg) in a factorial arrangement with 3 vaccine (V) protocols; no injection (0 × V), a single 2 mL injection of a Lawsonia intracellularis vaccine at day 14 (1 × V), or 2 mL injections of the same vaccine at days 0 and 7 (2 × V). An adjustment diet with no supplemental D was fed for 1 wk, then assigned D diets for 2 wk (P2). After P2, all pigs were phase-fed standard diets (D = 280 IU/kg) to assess subsequent growth to 115 kg. No differences due to D supplements or vaccination protocol were detected in ADG (0.233 ± 0.021 kg/d) or GF (0.642 ± 0.028 kg/d) over the 21-d nursery trial; however, ADFI was lower (P &lt; 0.10) in pigs fed D levels of 0 vs. 100 and 800 (0.340 vs. 0.375, 0.372 ± 0.027 kg/d). Bone mineral content (g) from whole-body dual energy X-ray absorptiometry scans at 9 wk (n = 4 pigs/treatment) was lower in pigs fed 0 vs. 100 and 800 IU of D (287 vs. 325, 323 ± 34.1 g/pig). Growth from nursery to 115 kg was lower (P &lt; 0.01) in pigs fed D levels of 0 vs.100 and 800 (0.828 vs. 0.876, 0.889 ± 0.021 kg/d). At market, approximately two-thirds of pigs showed positive L. intracellularis serology titers regardless of treatment. Limited evidence for D-mediation of an immune challenge using the vaccination protocols may be a consequence of limited vaccine effects on growth in the nursery and seroconversion of most pigs to L. intracellularis by market.
Archipelago-Wide Patterns of Colonization and Speciation Among an Endemic Radiation of Galápagos Land Snails
Authors: Phillips John G , Linscott T Mason , Rankin Andrew M , Kraemer Andrew C , Shoobs Nathaniel F , Parent Christine E 
Published: November 2019

AbstractNewly arrived species on young or remote islands are likely to encounter less predation and competition than source populations on continental landmasses. The associated ecological release might facilitate divergence and speciation as colonizing lineages fill previously unoccupied niche space. Characterizing the sequence and timing of colonization on islands represents the first step in determining the relative contributions of geographical isolation and ecological factors in lineage diversification. Herein, we use genome-scale data to estimate timing of colonization in Naesiotus snails to the Galápagos islands from mainland South America. We test inter-island patterns of colonization and within-island radiations to understand their contribution to community assembly. Partly contradicting previously published topologies, phylogenetic reconstructions suggest that most Naesiotus species form island-specific clades, with within-island speciation dominating cladogenesis. Galápagos Naesiotus also adhere to the island progression rule, with colonization proceeding from old to young islands and within-island diversification occurring earlier on older islands. Our work provides a framework for evaluating the contribution of colonization and in situ speciation to the diversity of other Galápagos lineages.
Periacetabular osteotomy using an imageless computer-assisted navigation system: a new surgical technique
Authors: Hooper Jessica M , Mays Rachel R , Poultsides Lazaros A , Castaneda Pablo G , Muir Jeffrey M , Kamath Atul F 
Published: November 2019

AbstractPeriacetabular osteotomy (PAO) is an effective surgical treatment for hip dysplasia. The goal of PAO is to reorient the acetabulum to improve joint stability, lessen contact stresses and slow the development of hip arthrosis. During PAO, the acetabulum is repositioned to adequately cover the femoral head. PAO preserves the weight-bearing posterior column of the pelvis, maintains the acetabular blood supply and retains the hip abductor musculature. The surgical technique needed to perform PAO is technically demanding, with correct repositioning of the acetabulum the most important—and challenging—aspect of the procedure. Imageless navigation has proven useful in other technically challenging surgeries, although its use in PAO has not yet been investigated. We have modified the standard technique for PAO to include the use of an imageless navigation system to confirm acetabular fragment position following osteotomy. Here, we describe the surgical technique and discuss the potential of this modified technique to improve patient-related outcomes.
Monocytic Maturation Induced by FLT3 Inhibitor Therapy of Acute Myeloid Leukemia: Morphologic and Immunophenotypic Characteristics
Authors: Arries Cade D , Yohe Sophia L 
Published: November 2019

Abstract

Background
FMS-like tyrosine kinase-3 (FLT3-ITD) mutations are some of the most common mutations in acute myeloid leukemia (AML), and patient outcomes have improved since the advent of tyrosine kinase inhibitors. First, granulocytic differentiation was described in FLT3-positive AML treated with FLT3 inhibitors, and more recently, monocytic differentiation was reported.

Methods
Two patients with myelomonocytic cells in their bone marrow were identified during routine follow-up after AML treatment that included FLT3 inhibitors. The bone marrow study was done as standard of care.

Results
Both patients had FLT3-ITD+ AML and showed an atypical maturing monocytic cell population and a decrease in the leukemic blast cell population after FLT3 inhibitor therapy. Concurrent genetic testing revealed persistent genetic abnormalities.

Conclusions
These cases illustrate monocytic maturation in FLT3+ AML after FLT3 inhibitor treatment. It is critical for pathologists and clinicians to be aware of the differentiation phenomenon, as these patients have persistent molecular abnormalities despite response to treatment and normalization of blast counts.
Chemical evolution with rotating massive star yields II. A new assessment of the solar s- and r- process components
Authors: Prantzos N , Abia C , Cristallo S , Limongi M , Chieffi A 
Published: November 2019

Abstract
The decomposition of the Solar system abundances of heavy isotopes into their s- and r- components plays a key role in our understanding of the corresponding nuclear processes and the physics and evolution of their astrophysical sites. We present a new method for determining the s- and r- components of the Solar system abundances, fully consistent with our current understanding of stellar nucleosynthesis and galactic chemical evolution. The method is based on a study of the evolution of the solar neighborhood with a state-of-the-art 1-zone model, using recent yields of low and intermediate mass stars as well as of massive rotating stars. We compare our results with previous studies and we provide tables with the isotopic and elemental contributions of the s- and r-processes to the Solar system composition.
Algorithm-improved high-speed and non-invasive confocal Raman imaging of 2D materials
Authors: Nair Sachin , Gao Jun , Yao Qirong , Duits Michael H G , Otto Cees , Mugele Frieder 
Published: November 2019

Abstract
Confocal Raman microscopy is important for characterizing 2D materials, but its low throughput significantly hinders its applications. For metastable materials such as graphene oxide (GO), the low throughput is aggravated by the requirement of extremely low laser dose to avoid sample damage. Here we introduce algorithm-improved confocal Raman microscopy (ai-CRM), which increases the Raman scanning rate by one to two orders of magnitude with respect to state-of-the-art works for a variety of 2D materials. Meanwhile, GO can be imaged at a laser dose that is two to three orders of magnitude lower than previously reported, such that laser-induced variations of the material properties can be avoided. ai-CRM also enables fast and spatially resolved quantitative analysis, and is readily extended to 3D mapping of composite materials. Since ai-CRM is based on general mathematical principles, it is cost-effective, facile to implement and universally applicable to other hyperspectral imaging methods.
Functional requirement of terminal inverted repeats for efficient ProtoRAG activity reveals the early evolution of V(D)J recombination
Authors: Tao Xin , Yuan Shaochun , Chen Fan , Gao Xiaoman , Wang Xinli , Yu Wenjuan , Liu Song , Huang Ziwen , Chen Shangwu , Xu Anlong 
Published: November 2019

Abstract
The discovery of ProtoRAG in amphioxus indicated that vertebrate RAG recombinases originated from an ancient transposon. However, the sequences of ProtoRAG terminal inverted repeats (TIRs) were obviously dissimilar to the consensus sequence of mouse 12/23RSS and recombination mediated by ProtoRAG or RAG made them incompatible with each other. Thus, it is difficult to determine whether or how 12/23RSS persisted in the vertebrate RAG system that evolved from the TIRs of ancient RAG transposons. Here, we found that the activity of ProtoRAG is highly dependent on its asymmetric 5′TIR and 3′TIR, which are composed of conserved TR1 and TR5 elements and a partially conserved TRsp element of 27/31 bp to separate them. Similar to the requirements for the recombination signal sequences (RSSs) of RAG recombinase, the first CAC in TR1, the three dinucleotides in TR5 and the specific length of the partially conserved TRsp are important for the efficient recombination activity of ProtoRAG. In addition, the homologous sequences flanking the signal sequences facilitate ProtoRAG- but not RAG-mediated recombination. In addition to the diverged TIRs, two differentiated functional domains in BbRAG1L were defined to coordinate with the divergence between TIRs and RSSs. One of these is the CTT* domain, which facilitates the specific TIR recognition of the BbRAGL complex, and the other is NBD*, which is responsible for DNA binding and the protein stabilization of the BbRAGL complex. Thus, our findings reveal that the functional requirement for ProtoRAG TIRs is similar to that for RSS in RAG-mediated recombination, which not only supports the common origin of ProtoRAG TIRs and RSSs from the asymmetric TIRs of ancient RAG transposons, but also reveals the development of RAG and RAG-like machineries during chordate evolution.
Nutritional interventions for autism spectrum disorder
Authors: Karhu Elisa , Zukerman Ryan , Eshraghi Rebecca S , Mittal Jeenu , Deth Richard C , Castejon Ana M , Trivedi Malav , Mittal Rahul , Eshraghi Adrien A 
Published: November 2019

AbstractAutism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental disorder with considerable clinical heterogeneity. With no cure for the disorder, treatments commonly center around speech and behavioral therapies to improve the characteristic social, behavioral, and communicative symptoms of ASD. Gastrointestinal disturbances are commonly encountered comorbidities that are thought to be not only another symptom of ASD but to also play an active role in modulating the expression of social and behavioral symptoms. Therefore, nutritional interventions are used by a majority of those with ASD both with and without clinical supervision to alleviate gastrointestinal and behavioral symptoms. Despite a considerable interest in dietary interventions, no consensus exists regarding optimal nutritional therapy. Thus, patients and physicians are left to choose from a myriad of dietary protocols. This review, summarizes the state of the current clinical and experimental literature on nutritional interventions for ASD, including gluten-free and casein-free, ketogenic, and specific carbohydrate diets, as well as probiotics, polyunsaturated fatty acids, and dietary supplements (vitamins A, C, B6, and B12; magnesium and folate).
Microstructural and physiological responses to cadmium stress under different nitrogen levels in Populus cathayana females and males
Authors: Liu Miao , Bi Jingwen , Liu Xiucheng , Kang Jieyu , Korpelainen Helena , Niinemets Ülo , Li Chunyang 
Published: November 2019

AbstractAlthough increasing attention has been paid to the relationships between heavy metal and nitrogen (N) availability, the mechanism underlying adaptation to cadmium (Cd) stress in dioecious plants has been largely overlooked. This study examined Cd accumulation, translocation and allocation among tissues and cellular compartments in Populus cathayana Rehder females and males. Both leaf Cd accumulation and root-to-shoot Cd translocation were significantly greater in females than in males under a normal N supply, but they were reduced in females and enhanced in males under N deficiency. The genes related to Cd uptake and translocation, HMA2, YSL2 and ZIP2, were strongly induced by Cd stress in female roots and in males under a normal N supply. Cadmium largely accumulated in the leaf blades of females and in the leaf veins of males under a normal N supply, while the contrary was true under N deficiency. Furthermore, Cd was mainly distributed in the leaf epidermis and spongy tissues of males, and in the leaf palisade tissues of females. Nitrogen deficiency increased Cd allocation to the spongy tissues of female leaves and to the palisade tissues of males. In roots, Cd was preferentially distributed to the epidermis and cortices in both sexes, and also to the vascular tissues of females under a normal N supply but not under N deficiency. These results suggested that males possess better Cd tolerance compared with females, even under N deficiency, which is associated with their reduced root-to-shoot Cd translocation, specific Cd distribution in organic and/or cellular compartments, and enhanced antioxidation and ion homeostasis. Our study also provides new insights into engineering woody plants for phytoremediation.
Phacoemulsification Versus Phacotrabeculectomy in Primary Angle-closure Glaucoma With Cataract: Long-Term Clinical Outcomes
Authors: Hansapinyo Linda , Choy Bonnie N.K. , Lai Jimmy S.M. , Tham Clement C. 
Published: November 2019

Precis:Phacotrabeculectomy was more effective in reducing intraocular pressure (IOP) and glaucoma drugs than phacoemulsification alone in primary angle-closure glaucoma (PACG) eyes with cataract but was associated with more postoperative complications, up to 5 years after surgery.Purpose:The purpose of this study was to compare long-term clinical outcomes of phacoemulsification versus phacotrabeculectomy in PACG eyes with cataract.Patients and Methods:The 2 initial prospective randomized controlled trials recruited PACG eyes with cataract using the same criteria and randomized these eyes to receiving either phacoemulsification or phacotrabeculectomy. Clinical data up to 5 years of follow-up were pooled for retrospective analysis.Results:Clinical data of 35 patients in the phacoemulsification group and 44 patients in the phacotrabeculectomy group were analyzed. At 5 years after surgery, the mean IOP was decreased by 20.7% and 29.5% from before surgery to 5 years after phacoemulsification and phacotrabeculectomy, respectively (P<0.001 for both groups). Phacotrabeculectomy was significantly more effective than phacoemulsification in reducing IOP up to 5 years after surgery (P<0.001). At 5 years, the mean number of glaucoma drugs required±1 SD was 1.6±1.2 in the phacoemulsification group, and 0.7±1.0 in the phacotrabeculectomy group (P=0.004). Phacotrabeculectomy was associated with more postoperative complications than phacoemulsification up to 5 years (25 complications in the phacotrabeculectomy group versus 6 in the phacoemulsification group,P<0.001).Conclusions:Phacoemulsification alone reduces IOP and the need for glaucoma drugs in PACG eyes with cataracts for up to 5 years. Phacotrabeculectomy was more effective in reducing IOP and glaucoma drugs than phacoemulsification alone but was associated with more postoperative complications, up to 5 years after surgery.