bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly selective diversion with proactive leakage management after low anterior resection for rectal cancer
Authors: Talboom K , Vogel I , Blok R D , Roodbeen S X , Ponsioen C Y , Bemelman W A , Hompes R , Tanis P J 
Published: January 2021

In this single center case series with nine percent primary diversion, 86 of 94 patients alive and with complete follow-up at one year had a functioning anastomosis. Seventy-five of the initial 99 patients never had a stoma.
Meaning: Highly selective fecal diversion in combination with proactive leakage management, low anastomoses can be preserved safely, and the majority of patients will be spared all disadvantages of a diverting stoma.
EYA2 upregulates miR-93 to promote tumorigenesis of breast cancer by targeting and inhibiting the STING signaling pathway
Authors: Ren Lishen , Guo Dongrui , Wan Xiaohui , Qu Rongfeng 
Published: January 2021

Abstract
Herein, we used DIANA TOOLS, gene expression profiling interactive analysis and other bioinformatics databases to predict regulatory pathways in breast cancer. Accordingly, we clarified the regulatory mechanism of eyes absent family of protein (EYA2) on miR-93 expression to aggravate breast cancer, which was involved with the STING signaling pathway. Cholecystokinin octapeptide assay, scratch test, Transwell assay and flow cytometry were applied to detect cell viability, migration, invasion and apoptosis. The experimental data found that EYA2 was highly expressed in breast cancer tissues and cells and associated with poor prognosis. Overexpression of miR-93 in breast cancer was positively correlated with EYA2. EYA2 promoted miR-93 expression, advanced breast cancer cell proliferation and inhibited their apoptosis. Results of luciferase assay showed that miR-93 was enriched in the STING 3’UTR (untranslated region). Furthermore, knockdown of EYA2 inhibited the expression of miR-93, promoted the expression of STING and inhibited the tumor growth. In response to EYA2 knockdown, the expression of IFN-β and interferon-stimulated gene was increased, and PD-L1 was decreased. In addition, the phosphorylation level of TANK-binding kinase 1 and interferon regulatory factor 3 was enhanced, the percentage of myeloid-derived suppressor cells in blood was reduced, and secretion of IFN-β and IL-12 was enhanced. In conclusion, EYA2 upregulates miR-93 expression and promotes malignancy of breast cancer by targeting and inhibiting the STING signaling pathway.
The Transcription Factor Shox2 Shapes Neuron Firing Properties and Suppresses Seizures by Regulation of Key Ion Channels in Thalamocortical Neurons
Authors: Yu Diankun , Febbo Isabella G , Maroteaux Matthieu J , Wang Hanyun , Song Yingnan , Han Xiao , Sun Cheng , Meyer Emily E , Rowe Stuart , Chen Yiping , Canavier Carmen C , Schrader Laura A 
Published: January 2021

Abstract
Thalamocortical neurons (TCNs) play a critical role in the maintenance of thalamocortical oscillations, dysregulation of which can result in certain types of seizures. Precise control over firing rates of TCNs is foundational to these oscillations, yet the transcriptional mechanisms that constrain these firing rates remain elusive. We hypothesized that Shox2 is a transcriptional regulator of ion channels important for TCN function and that loss of Shox2 alters firing frequency and activity, ultimately perturbing thalamocortical oscillations into an epilepsy-prone state. In this study, we used RNA sequencing and quantitative PCR of control and Shox2 knockout mice to determine Shox2-affected genes and revealed a network of ion channel genes important for neuronal firing properties. Protein regulation was confirmed by Western blotting, and electrophysiological recordings showed that Shox2 KO impacted the firing properties of a subpopulation of TCNs. Computational modeling showed that disruption of these conductances in a manner similar to Shox2’s effects modulated frequency of oscillations and could convert sleep spindles to near spike and wave activity, which are a hallmark for absence epilepsy. Finally, Shox2 KO mice were more susceptible to pilocarpine-induced seizures. Overall, these results reveal Shox2 as a transcription factor important for TCN function in adult mouse thalamus.
Taxonomic and functional adaption of the gastrointestinal microbiome of goats kept at high altitude (4800 m) under intensive or extensive rearing conditions
Authors: Zhang Ke , He Chong , Xu Yangbin , Zhang Chenguang , Li Chao , Jing Xu , Wang Meili , Yang Yuxin , Suo Langda , Kalds Peter , Song Jiuzhou , Wang Xiaolong , Brugger Daniel , Wu Yujiang , Chen Yulin 
Published: January 2021

ABSTRACT
The gut microbiota composition is influenced by the diet as well as the environment in both wild and domestic animals. We studied the effects of two feeding systems on the rumen and hindgut microbiome of semi-feral Tibetan goats kept at high altitude (∼4800 m) using 16S rRNA gene and metagenomic sequencing. Intensive drylot feeding resulted in significantly higher zootechnical performance, narrower ruminal acetate: propionate ratios and a drop in the average rumen pH at slaughter to ∼5.04. Hindgut microbial adaption appeared to be more diverse in the drylot group suggesting a higher influx of undegraded complex non-starch polysaccharides from the rumen. Despite their higher fiber levels in the diet, grazing goats exhibited lower counts of Methanobrevibacter and genes associated with the hydrogenotrophic methanogenesis pathway, presumably reflecting the scarce dietary conditions (low energy density) when rearing goats on pasture from extreme alpine environments. These conditions appeared to promote a relevant abundance of bacitracin genes. In parallel, we recognized a significant increase in the abundance of antibiotic resistance genes in the digestive tracts of drylot animals. In summary, this study provides a deeper insight into the metataxonomic and functional adaption of the gastrointestinal microbiome of goats subject to intensive drylot and extensive pasture rearing conditions at high altitude.
THE COHESIVE POPULATION GENETICS OF MOLECULAR DRIVE
Authors: Ohta Tomoko , Dover Gabriel A 
Published: January 2021

ABSTRACT
The long-term population genetics of multigene families is influenced by several biased and unbiased mechanisms of nonreciprocal exchanges (gene conversion, unequal exchanges, transposition) between member genes, often distributed on several chromosomes. These mechanisms cause fluctuations in the copy number of variant genes in an individual and lead to a gradual replacement of an original family of n genes (A) in N number of individuals by a variant gene (a). The process for spreading a variant gene through a family and through a population is called molecular drive. Consideration of the known slow rates of nonreciprocal exchanges predicts that the population variance in the copy number of gene a per individual is small at any given generation during molecular drive. Genotypes at a given generation are expected only to range over a small section of all possible genotypes from one extreme (n number of A) to the other (n number of a). A theory is developed for estimating the size of the population variance by using the concept of identity coefficients. In particular, the variance in the course of spreading of a single mutant gene of a multigene family was investigated in detail, and the theory of identity coefficients at the state of steady decay of genetic variability proved to be useful. Monte Carlo simulations and numerical analysis based on realistic rates of exchange in families of known size reveal the correctness of the theoretical prediction and also assess the effect of bias in turnover. The population dynamics of molecular drive in gradually increasing the mean copy number of a variant gene without the generation of a large variance (population cohesion) is of significance regarding potential interactions between natural selection and molecular drive.
The relationship between development assistance for health and public health financing in 134 countries between 2000 and 2015
Authors: Patenaude Bryan N 
Published: January 2021

Abstract
This paper utilizes causal time-series and panel techniques to examine the relationship between development assistance for health (DAH) and domestic health spending, both public and private, in 134 countries between 2000 and 2015. Data on 237 656 donor transactions from the Institute for Health Metrics and Evaluation’s DAH and Health Expenditure datasets are merged with economic, demographic and health data from the World Bank Databank and World Health Organization’s Global Health Observatory. Arellano–Bond system GMM estimation is used to assess the effect of changes in DAH on domestic health spending and health outcomes. Analyses are conducted for the entire health sector and separately for HIV, TB and malaria financing. Results show that DAH had no significant impact on overall domestic public health investment. For HIV-specific investments, a $1 increase in on-budget DAH was associated with a $0.12 increase in government spending for HIV. For the private sector, $1 in DAH is associated with a $0.60 and $0.03 increase in prepaid private spending overall and for malaria, with no significant impact on HIV spending. Results demonstrate that a 1% increase in public financing reduced under-5 mortality by 0.025%, while a 1% increase in DAH had no significant effect on reducing under-5 mortality. The relationships between DAH and public health financing suggest that malaria and HIV-specific crowding-in effects are offset by crowding-out effects in other unobserved health sectors. The results also suggest policies that crowd-in public financing will likely have larger impacts on health outcomes than DAH investments that do not crowd-in public spending.
Temperature-dependent autoactivation associated with clinical variability of PDGFRB Asn666 substitutions
Authors: Bredrup Cecilie , Cristea Ileana , Safieh Leen Abu , Di Maria Emilio , Gjertsen Bjørn Tore , Tveit Kåre Steinar , Thu Frode , Bull Nils , Edward Deepak P , Hennekam Raoul C M , Høvding Gunnar , Haugen Olav H , Houge Gunnar , Rødahl Eyvind , Bruland Ove 
Published: January 2021

Abstract
Ocular pterygium-digital keloid dysplasia (OPDKD) presents in childhood with ingrowth of vascularized connective tissue on the cornea leading to severely reduced vision. Later the patients develop keloids on digits but are otherwise healthy. The overgrowth in OPDKD affects body parts that typically have lower temperature than 37°C. We present evidence that OPDKD is associated with a temperature sensitive, activating substitution, p.(Asn666Tyr), in PDGFRB. Phosphorylation levels of PDGFRB and downstream targets were higher in OPDKD fibroblasts at 37°C but were further greatly increased at the average corneal temperature of 32°C. This suggests that the substitution cause significant constitutive autoactivation mainly at lower temperature.
In contrast, a different substitution in the same codon, p.(Asn666Ser), is associated with Penttinen type of premature aging syndrome. This devastating condition is characterized by widespread tissue degeneration, including pronounced chronic ulcers and osteolytic resorption in distal limbs. In Penttinen syndrome fibroblasts, equal and high levels of phosphorylated PDGFRB was present at both 32°C and 37°C. This indicates that this substitution causes severe constitutive autoactivation of PDGFRB regardless of temperature. In line with this, most downstream targets were not affected by lower temperature. However, STAT1, important for tissue wasting, did show further increased phosphorylation at 32°C. Temperature-dependent autoactivation offers an explanation to the strikingly different clinical outcomes of substitutions in the Asn666 codon of PDGFRB.
Humanitarian challenges and the targeting of civilian infrastructure in the Yemen war
Authors: Sowers Jeannie , Weinthal Erika 
Published: January 2021

Abstract
Many modern conflicts, from Iraq to Yemen, have emerged as brutal wars in which state and non-state actors directly and indirectly target a wide array of civilian infrastructures, including water, energy and food systems. Similar to many twentieth-century wars, a common feature of the wars in the Middle East and North Africa in the twenty-first century has been the ‘civilianization’ of war, as civilian casualties far outnumbered battlefield deaths. We explore the targeting of civilian infrastructures in the Yemeni war (2011–2019) to explicate the connections between conflict, hunger and disease. We draw upon interviews with UN and humanitarian organizations, an original database tracking civilian infrastructure destruction, and a variety of print sources to document the extent and spatial distribution of the targeting of water, energy, agricultural and health systems in Yemen. We elucidate how the conduct of the Yemeni war has undermined human security and livelihoods and has created ethical, logistical and organizational challenges for humanitarian organizations and for advancing peacebuilding efforts. We find that after the 2011 popular uprising, some non-state actors targeted the energy sector; however, the scope and intensity of wartime targeting of civilian objects, particularly those associated with agriculture, fisheries and health, increased significantly once the Saudi-led coalition entered the war in 2015. Loss of livelihoods, internal displacement, currency depreciation, and blockades and sieges further intensified the wartime spread of hunger and disease. The targeting of civilian infrastructures significantly hinders peacebuilding efforts to restore basic services, rebuild livelihoods and strengthen governance mechanisms.
An uncommon cause of massive haemothorax and treatment under cardiopulmonary bypass
Authors: Alptekin Erkul Gulen Sezer , Erkul Sinan , Parlar Ali İhsan , Çekirdekçi Ahmet 
Published: January 2021

Abstract
Pulmonary sequestration is defined as nonfunctioning lung tissue that is not in normal continuity with the tracheobronchial tree and that has a systemic arterial blood supply. Herein, we aimed to present a case of a 34-year-old male patient who had massive left-sided haemothorax on admission due to a giant intralobar pulmonary sequestration. An emergent repair was performed under cardiopulmonary bypass with axillofemoral cannulation.
A Menagerie of SU(2)-Cyclic 3-Manifolds
Authors: Sivek Steven , Zentner Raphael 
Published: January 2021

Abstract
We classify $SU(2)$-cyclic and $SU(2)$-abelian 3-manifolds, for which every representation of the fundamental group into $SU(2)$ has cyclic or abelian image, respectively, among geometric 3-manifolds that are not hyperbolic. As an application, we give examples of hyperbolic 3-manifolds that do not admit degree-1 maps to any Seifert Fibered manifold other than $S^3$ or a lens space. We also produce infinitely many one-cusped hyperbolic manifolds with at least four $SU(2)$-cyclic Dehn fillings, one more than the number of cyclic fillings allowed by the cyclic surgery theorem.
Asymptotics for Averages over Classical Orthogonal Ensembles
Authors: Claeys Tom , Glesner Gabriel , Minakov Alexander , Yang Meng 
Published: January 2021

AbstractWe study the averages of multiplicative eigenvalue statistics in ensembles of orthogonal Haar-distributed matrices, which can alternatively be written as Toeplitz+Hankel determinants. We obtain new asymptotics for symbols with Fisher–Hartwig singularities in cases where some of the singularities merge together and for symbols with a gap or an emerging gap. We obtain these asymptotics by relying on known analogous results in the unitary group and on asymptotics for associated orthogonal polynomials on the unit circle. As consequences of our results, we derive asymptotics for gap probabilities in the circular orthogonal and symplectic ensembles and an upper bound for the global eigenvalue rigidity in the orthogonal ensembles.
Conical Metrics on Riemann Surfaces, II: Spherical Metrics
Authors: Mazzeo Rafe , Zhu Xuwen 
Published: January 2021

Abstract
We continue our study, initiated in [34], of Riemann surfaces with constant curvature and isolated conic singularities. Using the machinery developed in that earlier paper of extended configuration families of simple divisors, we study the existence and deformation theory for spherical conic metrics with some or all of the cone angles greater than $2\pi $. Deformations are obstructed precisely when the number $2$ lies in the spectrum of the Friedrichs extension of the Laplacian. Our main result is that, in this case, it is possible to find a smooth local moduli space of solutions by allowing the cone points to split. This analytic fact reflects geometric constructions in [37, 38].
Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect
Authors: Lisco Andrea , Ye Peiying , Wong Chun-Shu , Pei Luxin , Hsu Amy P , Mace Emily M , Orange Jordan S , Lage Silvia Lucena , Ward Addison Jon , Migueles Stephen A , Connors Mark , Anderson Megan V , Buckner Clarisa M , Moir Susan , Rupert Adam , Dulau-Florea Alina , Ogbogu Princess , Timberlake Dylan , Notarangelo Luigi D , Pittaluga Stefania , Abraham Roshini S , Sereti Irini 
Published: January 2021

Abstract
CD4 expression identifies a subset of mature T cells primarily assisting the germinal center reaction and contributing to CD8+ T-cell and B-cell activation, functions, and longevity. Herein, we present a family in which a novel variant disrupting the translation-initiation codon of the CD4 gene resulted in complete loss of membrane and plasma soluble CD4 in peripheral blood, lymph node, bone marrow, skin, and ileum of a homozygous proband. This inherited CD4 knockout disease illustrates the clinical and immunological features of a complete deficiency of any functional component of CD4 and its similarities and differences with other clinical models of primary or acquired loss of CD4+ T cells.
Regulation of the Acute Sickness Response by the P2RX7 Receptor
Authors: Li Hui , Cvejic Erin , Gu Ben , Vollmer-Conna Ute , Hickie Ian , Wakefield Denis , Davenport Tracey , Wiley James , Lloyd Andrew R 
Published: January 2021

Abstract

Background
The acute sickness response to infection is a stereotyped set of illness manifestations initiated by proinflammatory signals in the periphery but mediated centrally. P2RX7 is a highly polymorphic gene encoding an ATP-gated cationic pore, widely expressed on immune cells and the brain, and regulating the NLRP3 inflammasome, as well as diverse neural functions.

Methods
Associations between P2RX7 genotype, pore activity, and illness manifestations were examined in a cohort with acute viral and bacterial infections (n = 484). Genotyping of 12 P2RX7 function-modifying single-nucleotide polymorphisms (SNPs) was used to identify haplotypes and diplotypes. Leucocyte pore activity was measured by uptake of the fluorescent dye, YO-PRO-1, and by ATP-induced interleukin-1β (IL-1β) release. Associations were sought with scores describing the symptom domains, or endophenotypes, derived from principal components analysis.

Results
Among the 12 SNPs, a 4-SNP haplotype block with 5 variants was found in 99.5% of the subjects. These haplotypes and diplotypes were closely associated with variations in pore activity and IL-1β production. Homozygous diplotypes were associated with overall illness severity as well as fatigue, pain, and mood disturbances.

Conclusions
P2RX7 signaling plays a significant role in the acute sickness response to infection, likely acting in both the immune system and the brain.
Pattern discovery, validation, and online experiments: a methodology for discovering television shows for public health announcements
Authors: Barfar Arash , Padmanabhan Balaji 
Published: January 2021

Abstract

Objective
Public Health Announcements (PHAs) on television are a means of raising awareness about risk behaviors and chronic conditions. PHAs’ scarce airtime puts stress on their target audience reach. We seek to help health campaigns select television shows for their PHAs about smoking, binge drinking, drug overdose, obesity, diabetes, STDs, and other conditions using available statistics.

Materials and Methods
Using Nielsen’s TV viewership database for the entire US panel, we presented a novel show discovery methodology for PHAs that combined (i) pattern discovery from high-dimensional data (ii) nonparametric tests for validation, and (iii) online experiments on Facebook.

Results
The nonparametric tests verified the robustness of the discovered associations between the popularity of certain shows and health conditions. Findings from fifty (independent) online experiments (where our awareness messages were seen by nearly 1.5 million American adults) empirically demonstrated the value of the methodology.

Discussion
For 2016, the methodology identified several shows whose popularities were genuinely associated with certain health conditions, opening up the possibility of health agencies embracing both big data and large-scale experimentation to address an old problem in a new way.

Conclusion
Policy makers can repeatedly apply the methodology as new data streams in, with perhaps different feature sets, pattern discovery techniques, and online experiments running over longer periods. The comparatively lower initial investment in the methodology can pay off by identifying several shows for a potentially national television campaign. As simply a by-product, the initial investment also results in awareness messages that might reach millions of individuals.
A Reference Genome Assembly of American Bison,Bison bison bison
Authors: Oppenheimer Jonas , Rosen Benjamin D , Heaton Michael P , Vander Ley Brian L , Shafer Wade R , Schuetze Fred T , Stroud Brad , Kuehn Larry A , McClure Jennifer C , Barfield Jennifer P , Blackburn Harvey D , Kalbfleisch Theodore S , Bickhart Derek M , Davenport Kimberly M , Kuhn Kristen L , Green Richard E , Shapiro Beth , Smith Timothy P L 
Published: January 2021

AbstractBison are an icon of the American West and an ecologically, commercially, and culturally important species. Despite numbering in the hundreds of thousands today, conservation concerns remain for the species, including the impact on genetic diversity of a severe bottleneck around the turn of the 20th century and genetic introgression from domestic cattle. Genetic diversity and admixture are best evaluated at genome-wide scale, for which a high-quality reference is necessary. Here, we use trio binning of long reads from a bison–Simmental cattle (Bos taurus taurus) male F1 hybrid to sequence and assemble the genome of the American plains bison (Bison bison bison). The male haplotype genome is chromosome-scale, with a total length of 2.65 Gb across 775 scaffolds (839 contigs) and a scaffold N50 of 87.8 Mb. Our bison genome is ~13× more contiguous overall and ~3400× more contiguous at the contig level than the current bison reference genome. The bison genome sequence presented here (ARS-UCSC_bison1.0) will enable new research into the evolutionary history of this iconic megafauna species and provide a new tool for the management of bison populations in federal and commercial herds.