bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus
Authors: Anthony S. J. , Gilardi K. , Menachery V. D. , Goldstein T. , Ssebide B. , Mbabazi R. , Navarrete-Macias I. , Liang E. , Wells H. , Hicks A. , Petrosov A. , Byarugaba D. K. , Debbink K. , Dinnon K. H. , Scobey T. , Randell S. H. , Yount B. L. , Cranfield M. , Johnson C. K. , Baric R. S. , Lipkin W. I. , Mazet J. A. K. 
Published: April 2017

ABSTRACT

The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family
Vespertilionidae
. Here, we describe a MERS-like CoV identified from a
Pipistrellus cf. hesperidus
bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans.

IMPORTANCE
Global surveillance efforts for undiscovered viruses are an important component of pandemic prevention initiatives. These surveys can be useful for finding novel viruses and for gaining insights into the ecological and evolutionary factors driving viral diversity; however, finding a viral sequence is not sufficient to determine whether it can infect people (i.e., poses a zoonotic threat). Here, we investigated the specific zoonotic risk of a MERS-like coronavirus (PREDICT/PDF-2180) identified in a bat from Uganda and showed that, despite being closely related to MERS-CoV, it is unlikely to pose a threat to humans. We suggest that this approach constitutes an appropriate strategy for beginning to determine the zoonotic potential of wildlife viruses. By showing that PREDICT/PDF-2180 does not infect cells that express the functional receptor for MERS-CoV, we further show that recombination was likely to be the critical step that allowed MERS to emerge in humans.
Are national policies on global health in fact national policies on global health governance? A comparison of policy designs from Norway and Switzerland
Authors: Jones Catherine M , Clavier Carole , Potvin Louise 
Published: April 2017

BackgroundSince the signing of the Oslo Ministerial Declaration in 2007, the idea that foreign policy formulation should include health considerations has gained traction on the United Nations agenda as evidenced by annual General Assembly resolutions on global health and foreign policy. The adoption of national policies on global health (NPGH) is one way that some member states integrate health and foreign policymaking. This paper explores what these policies intend to do and how countries plan to do it.MethodsUsing a most similar systems design, we carried out a comparative study of two policy documents formally adopted in 2012. We conducted a directed qualitative content analysis of the NorwegianWhite Paper on Global health in foreign and development policyand theSwiss Health Foreign Policyusing Schneider and Ingram's policy design framework. After replicating analysis methods for each document, we analysed them side by side to explore the commonalities and differences across elements of NPGH design.ResultsAnalyses indicate that NPGH expect to influence change outside their borders. Targeting the international level, they aim to affect policy venues, multilateral partnerships and international institutions. Instruments for supporting desired changes are primarily those of health diplomacy, proposed as a tool for negotiating interests and objectives for global health between multiple sectors, used internally in Switzerland and externally in Norway.ConclusionFindings suggest that NPGH designs contribute to constructing the global health governance system by identifying it as a policy target, and policy instruments may elude the health sector actors unless implementation rules explicitly include them. Research should explore how future NPGH designs may construct different kinds of targets as politicised groups of actors on which national governments seek to exercise influence for global health decision-making.
Countdown to 2015: an analysis of donor funding for prenatal and neonatal health, 2003–2013
Authors: Pitt Catherine , Grollman Christopher , Martínez-Álvarez Melisa , Arregoces Leonardo , Lawn Joy E , Borghi Josephine 
Published: April 2017

BackgroundIn 2015, 5.3 million babies died in the third trimester of pregnancy and first month following birth. Progress in reducing neonatal mortality and stillbirth rates has lagged behind the substantial progress in reducing postneonatal and maternal mortality rates. The benefits to prenatal and neonatal health (PNH) from maternal and child health investments cannot be assumed.MethodsWe analysed donor funding for PNH over the period 2003–2013. We used an exhaustive key term search followed by manual review and classification to identify official development assistance and private grant (ODA+) disbursement records in the Countdown to 2015 ODA+ Database.ResultsThe value of ODA+ mentioning PNH or an activity that would directly benefit PNH increased from $105 million in 2003 to $1465 million in 2013, but this included a 3% decline between 2012 and 2013. Projects exclusively benefitting PNH reached just $6 million in 2013. Records mentioning PNH accounted for 3% of the $2708 million disbursed in 2003 for maternal, newborn and child health (MNCH) and increased to 13% of the $9287 million disbursed for MNCH in 2013. In 11 years, only nine records ($6 million) mentioned stillbirth, miscarriage, or the fetus, although the two leading infectious causes of stillbirth were mentioned in records worth $832 million. The USA disbursed the most ODA+ mentioning PNH ($2848 million, 40% of the total) and Unicef disbursed the most ODA+ exclusively benefitting PNH ($18 million, 30%). We found evidence that funding mentioning and exclusively benefitting PNH was targeted to countries with greater economic needs, but the evidence of targeting to health needs was weak and inconsistent.ConclusionsNewborn health rose substantially on the global agenda between 2003 and 2013, but prenatal health received minimal attention in donor funding decisions. Declines in 2013 and persistently low funding exclusively benefitting PNH indicate a need for caution and continued monitoring of donors' support for newborn health.
Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants
Authors: Undre Nasrullah , Dickinson James 
Published: April 2017

ObjectiveTacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants.DesignA phase 1, open-label, single-dose, cross-over study.SettingA single clinical research unit.ParticipantsIn total, 20 male participants, 18–55 years old, entered and completed the study.InterventionsAll participants received nasogastric administration of tacrolimus 10 mg suspension in treatment period 1, with randomisation to oral administration of suspension or intact capsules in periods 2 and 3. Blood concentration–time profile over 144 hours was used to estimate pharmacokinetic parameters.Primary and secondary outcome measuresPrimary end point: relative bioavailability of prolonged-release intact capsule versus oral or nasogastric administration of prolonged-release tacrolimus suspension (area under the concentration–time curve (AUC) from time 0 to infinity post-tacrolimus dose (AUC0–∞); AUC measured until the last quantifiable concentration (AUC0–tz); maximum observed concentration (Cmax); time to Cmax(Tmax)). Tolerability was assessed throughout the study.ResultsRelative bioavailability of prolonged-release tacrolimus suspension administered orally was similar to intact capsules, with a ratio of least-square means for AUC0–tzand AUC0–∞of 1.05 (90% CI 0.96 to 1.14). Bioavailability was lower with suspension administered via a nasogastric tube versus intact capsules (17%; ratio 0.83; CI 0.76 to 0.92). Cmaxwas higher for oral and nasogastric suspension (30% and 28%, respectively), and median Tmaxwas shorter (difference 1.0 and 1.5 hours postdose, respectively) versus intact capsules (2.0 hours). Single 10 mg doses of tacrolimus were well tolerated.ConclusionsCompared with intact capsules, the rate of absorption of prolonged-release tacrolimus from suspension was faster, leading to higher peak blood concentrations and shorter time to peak; relative bioavailability was similar with suspension administered orally.
Assessment of supergene uranium-vanadium anomalies, Meob Bay deposit, Namibia
Authors: Bowell R. J. , Davies A. A. 
Published: April 2017

Extensive surficial uranium mineralization has been identified in the Namib Desert in central Namibia. The mineralization comprises of uranium-rich zones in excess of 500 ppm for more than 3 m in tertiary sediment channels within the Kalahari succession. In places zones over 10 000 ppm over 3 m were observed in the near surface sediments. The mineralization is unusual in that it is entirely within the recent sands and is unconnected to any bedrock anomalies indicating transport of uranium by supergene processes.
A reconnaissance level exploration program has been completed to determine the geological extent and controls on such mineralization and use this to determine potential viability of such deposits. Historic data combined with geophysical data were used to identify potentially high grade uranium anomalies including historically identified anomalies. In addition additional anomalies were also discovered during the course of the work.
Bedrock geology in the area comprises of high thorium granites with highly variable but generally low concentration of uranium that has complicated identification of potential radiometric targets requiring ground based studies to distinguish uranium anomalies. These are intruded into Kuiseb shists that most likely supplied vanadium. Detailed investigation of the identified uranium anomalies found mineralization was confined to the regolith only with high grade uranium (VI) mineralization confined to ferric oxide-rich aeolian sand horizons and black weathered biotite schist horizons, indicating the mineralization was likely of secondary origin.
The assessment of the geology and recent sedimentology indicates that the uranium source is likely to be from the Damara intrusives to the east of the field area with extensive hydrogeochemical mobilization of uranium post-uplift in the Cretaceous period. A complex uranium mineralogy in the sands indicates bi-modal formation of uranium with both oxidation and reduction mechanisms having some control on uranium precipitation in various parts of the deposit.
The mineralization demonstrates the dynamic geochemistry of uranium and the ability to concentrate the metal by entirely supergene processes. Although such deposits of this type are challenged to form a sufficiently large size to be considered economic, potential still exists to identify further high grade zones.
Procedural Content Generation for Game Props? A Study on the Effects on User Experience
Authors: Korn Oliver , Blatz Michael , Rees Adrian , Schaal Jakob , Schwind Valentin , Görlich Daniel 
Published: April 2017

This work demonstrates the potentials of procedural content generation (PCG) for games, focusing on the generation of specific graphic props (reefs) in an explorer game.
We briefly portray the state-of-the-art of PCG and compare various methods to create random patterns at runtime. Taking a step towards the game industry, we describe an actual game production and provide a detailed pseudocode implementation showing how Perlin or Simplex noise can be used efficiently.
In a comparative study, we investigate two alternative implementations of a decisive game prop: once created traditionally by artists and once generated by procedural algorithms. 41 test subjects played both implementations. The analysis shows that PCG can create a user experience that is significantly more realistic and at the same time perceived as more aesthetically pleasing. In addition, the ever-changing nature of the procedurally generated environments is preferred with high significance, especially by players aged 45 and above.
Musculoskeletal geometry accounts for apparent extrinsic representation of paw position in dorsal spinocerebellar tract
Authors: Chowdhury Raeed H. , Tresch Matthew C. , Miller Lee E. 
Published: April 2017

Proprioception, the sense of limb position and motion, arises from individual muscle receptors. An important question is how and where in the neuroaxis our high level “extrinsic” sense of limb movement originates. In the 1990s, a series of papers detailed the properties of neurons in the dorsal spinocerebellar tract (DSCT) of the cat. Despite their direct projections from sensory receptors, it appeared that half of these neurons had consistent, high-level tuning to paw position rather than to joint angles (or muscle lengths). These results suggested that many DSCT neurons compute paw position from lower level sensory information. We examined the contribution of musculoskeletal geometry to this apparent extrinsic representation by simulating a three-joint hindlimb with mono- and biarticular muscles, each providing a muscle spindlelike signal, modulated by the muscle length. We simulated neurons driven by randomly weighted combinations of these signals and moved the paw to different positions under two joint-covariance conditions similar to the original experiments. Our results paralleled those experiments in a number of respects: 1) Many neurons were tuned to paw position relative to the hip under both conditions. 2) The distribution of tuning was strongly bimodal, with most neurons driven by whole-leg flexion or extension. 3) The change in tuning between conditions clustered around zero (median absolute change ~20°). These results indicate that, at least for these constraint conditions, extrinsic-like representation can be achieved simply through musculoskeletal geometry and convergent muscle length inputs. Consequently, they suggest a reinterpretation of the earlier results may be required. NEW & NOTEWORTHY A classic experiment concluding that many dorsal spinocerebellar tract neurons encode paw position rather than joint angles has been cited by many studies as evidence for high-level computation occurring within a single synapse of the sensors. However, our study provides evidence that such a computation is not required to explain the results. Using simulation, we replicated many of the original results with purely random connectivity, suggesting that a reinterpretation of the classic experiment is needed.
Increased neuromuscular consistency in gait and balance after partnered, dance-based rehabilitation in Parkinson’s disease
Authors: Allen Jessica L. , McKay J. Lucas , Sawers Andrew , Hackney Madeleine E. , Ting Lena H. 
Published: April 2017

Here we examined changes in muscle coordination associated with improved motor performance after partnered, dance-based rehabilitation in individuals with mild to moderate idiopathic Parkinson’s disease. Using motor module (a.k.a. muscle synergy) analysis, we identified changes in the modular control of overground walking and standing reactive balance that accompanied clinically meaningful improvements in behavioral measures of balance, gait, and disease symptoms after 3 wk of daily Adapted Tango classes. In contrast to previous studies that revealed a positive association between motor module number and motor performance, none of the six participants in this pilot study increased motor module number despite improvements in behavioral measures of balance and gait performance. Instead, motor modules were more consistently recruited and distinctly organized immediately after rehabilitation, suggesting more reliable motor output. Furthermore, the pool of motor modules shared between walking and reactive balance increased after rehabilitation, suggesting greater generalizability of motor module function across tasks. Our work is the first to show that motor module distinctness, consistency, and generalizability are more sensitive to improvements in gait and balance function after short-term rehabilitation than motor module number. Moreover, as similar differences in motor module distinctness, consistency, and generalizability have been demonstrated previously in healthy young adults with and without long-term motor training, our work suggests commonalities in the structure of muscle coordination associated with differences in motor performance across the spectrum from motor impairment to expertise. NEW & NOTEWORTHY We demonstrate changes in neuromuscular control of gait and balance in individuals with Parkinson’s disease after short-term, dance-based rehabilitation. Our work is the first to show that motor module distinctness, consistency, and generalizability across gait and balance are more sensitive than motor module number to improvements in motor performance following short-term rehabilitation. Our results indicate commonalities in muscle coordination improvements associated with motor skill reacquisition due to rehabilitation and motor skill acquisition in healthy individuals.
The p53/p21 Complex Regulates Cancer Cell Invasion and Apoptosis by Targeting Bcl-2 Family Proteins
Authors: Kim Eun Mi , Jung Chan-Hun , Kim Jongdoo , Hwang Sang-Gu , Park Jong Kuk , Um Hong-Duck 
Published: April 2017

AbstractThe tumor suppressor p53 binds prosurvival Bcl-2 family proteins such as Bcl-w and Bcl-XL to liberate Bax, which in turn exerts proapoptotic or anti-invasive functions depending on stress context. On the basis of our previous finding that p53 interacts with p21, we investigated the possible involvement of p21 in these functions. Here, we report that although p53 can bind Bcl-w alone, it requires p21 to liberate Bax to suppress cell invasion and promote cell death. p21 bound Bcl-w, forming a p53/p21/Bcl-w complex in a manner that maintained all pairwise p53/p21, p21/Bcl-w, and p53/Bcl-w interactions. This allowed Bax liberation from the complex. Accordingly, a p53 derivative incapable of binding p21 failed to mediate radiotherapy-induced tumor cell death in mice. Bcl-XL also served as a target of the cooperative action of p53 and p21. Overall, our findings indicate that the p53/p21 complex rather than p53 itself regulates cell invasion and death by targeting Bcl-2 proteins. We propose that the p53/p21 complex is a functional unit that acts on multiple cell components, providing a new foundation for understanding the tumor-suppressing functions of p53 and p21. Cancer Res; 77(11); 3092–100. ©2017 AACR.
Thyroid-Stimulating Hormone, Thyroid Hormones, and Risk of Papillary Thyroid Cancer: A Nested Case–Control Study
Authors: Huang Huang , Rusiecki Jennifer , Zhao Nan , Chen Yingtai , Ma Shuangge , Yu Herbert , Ward Mary H. , Udelsman Robert , Zhang Yawei 
Published: April 2017

Abstract
Background: The effects of thyroid-stimulating hormone (TSH) and thyroid hormones on the development of human papillary thyroid cancer (PTC) remain poorly understood.
Methods: The study population consisted of 741 (341 women, 400 men) histologically confirmed PTC cases and 741 matched controls with prediagnostic serum samples stored in the Department of Defense Serum Repository. Concentrations of TSH, total T3, total T4, and free T4 were measured in serum samples. Conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI).
Results: The median time between blood draw and PTC diagnosis was 1,454 days. Compared with the middle tertile of TSH levels within the normal range, serum TSH levels below the normal range were associated with an elevated risk of PTC among women (OR, 3.74; 95% CI, 1.53–9.19) but not men. TSH levels above the normal range were associated with an increased risk of PTC among men (OR, 1.96; 95% CI, 1.04–3.66) but not women. The risk of PTC decreased with increasing TSH levels within the normal range among both men and women (Ptrend = 0.0005 and 0.041, respectively).
Conclusions: We found a significantly increased risk of PTC associated with TSH levels below the normal range among women and with TSH levels above the normal range among men. An inverse association between PTC and TSH levels within the normal range was observed among both men and women.
Impact: These results could have significant clinical implications for physicians who are managing patients with abnormal thyroid functions and those with thyroidectomy. Cancer Epidemiol Biomarkers Prev; 26(8); 1209–18. ©2017 AACR.