bluuebunny/crossref_metadata_2025_split huggingface dataset:
Directed evolution of a remarkably efficient Kdnase from a bacterial neuraminidase
Authors: Shamsi Kazem Abadi Saeideh , Deen Matthew C , Watson Jacqueline N , Shidmoossavee Fahimeh S , Bennet Andrew J 
Published: November 2019

AbstractN-acetylneuraminic acid (5-acetamido-3,5-dideoxy-d-glycero-d-galacto-non-2-ulosonic acid), which is the principal sialic acid family member of the non-2-ulosonic acids and their various derivatives, is often found at the terminal position on the glycan chains that adorn all vertebrate cells. This terminal position combined with subtle variations in structure and linkage to the underlying glycan chains between humans and other mammals points to the importance of this diverse group of nine-carbon sugars as indicators of the unique aspects of human evolution and is relevant to understanding an array of human conditions. Enzymes that catalyze the removal N-acetylneuraminic acid from glycoconjugates are called neuraminidases. However, despite their documented role in numerous diseases, due to the promiscuous activity of many neuraminidases, our knowledge of the functions and metabolism of many sialic acids and the effect of the attachment to cellular glycans is limited. To this end, through a concerted effort of generation of random and site-directed mutagenesis libraries, subsequent screens and positive and negative evolutionary selection protocols, we succeeded in identifying three enzyme variants of the neuraminidase from the soil bacterium Micromonospora viridifaciens with markedly altered specificity for the hydrolysis of natural Kdn (3-deoxy-d-glycero-d-galacto-non-2-ulosonic acid) glycosidic linkages compared to those of N-acetylneuraminic acid. These variants catalyze the hydrolysis of Kdn-containing disaccharides with catalytic efficiencies (second-order rate constants: kcat/Km) of greater than 105 M−1 s−1; the best variant displayed an efficiency of &gt;106 M−1 s−1 at its optimal pH.
Reduction of Tet2 exacerbates early stage Alzheimer’s pathology and cognitive impairments in 2×Tg-AD mice
Authors: Li Liping , Qiu Yisha , Miao Miao , Liu Zhitao , Li Wanyi , Zhu Yiyi , Wang Qinwen 
Published: November 2019

Abstract
Abnormal modification of 5-hydroxymethylcytosine (5hmC) is closely related to the occurrence of Alzheimer’s disease (AD). However, the role of 5hmC and its writers, ten-eleven translocation (Tet) proteins, in regulating the pathogenesis of AD remains largely unknown. We detected a significant decrease in 5hmC and Tet2 levels in the hippocampus of aged APPswe/PSEN1 double-transgenic (2×Tg-AD) mice that coincides with abundant amyloid-β (Aβ) plaque accumulation. On this basis, we examined the reduction of Tet2 expression in the hippocampus at early disease stages, which caused a decline of 5hmC levels and led young 2×Tg-AD mice to present with advanced stages of AD-related pathological hallmarks, including Aβ accumulation, GFAP-positive astrogliosis and Iba1-positive microglia overgrowth as well as the overproduction of pro-inflammatory factors. Additionally, the loss of Tet2 in the 2×Tg-AD mice at 5 months of age accelerated hippocampal-dependent learning and memory impairments compared to age-matched control 2×Tg-AD mice. In contrast, restoring Tet2 expression in adult neural stem cells isolated from aged 2×Tg-AD mice hippocampi increased 5hmC levels and increased their regenerative capacity, suggesting that Tet2 might be an exciting target for rejuvenating the brain during aging and AD. Further, hippocampal RNA sequencing data revealed that the expression of altered genes identified in both Tet2 knockdown and control 2×Tg-AD mice was significantly associated with inflammation response. Finally, we demonstrated that Tet2-mediated 5hmC epigenetic modifications regulate AD pathology by interacting with HDAC1. These results suggest a combined approach for the regulation and treatment of AD-related memory impairment and cognitive symptoms by increasing Tet2 via HDAC1 suppression.
Modified iliac spine wafer osteotomy for exposure during Bernese periacetabular osteotomy
Authors: Samuel Linsen T , Munim Mohammed , Acuña Alexander J , Sultan Assem A , Kamath Atul F 
Published: November 2019

AbstractThe Bernese periacetabular osteotomy (PAO) is a well-established procedure for the management of symptomatic hip dysplasia. The associated Smith–Petersen exposure offers excellent visualization of the acetabulum and control of acetabular osteotomy and mobilization. The traditional exposure of the true pelvis involves osteotomy of the iliac wing in order to mobilize the sartorial and inguinal ligament insertion. However, full osteotomy of the iliac spine may necessitate screw fixation if a relatively large segment of bone is included. A known complication with screw fixation of the iliac wing osteotomy involves failure of fixation and screw back out. Moreover, the screw may irritate the patient even in the setting of adequate fixation. A larger osteotomy may also injure the lateral femoral cutaneous nerve (LFCN) as it travels near the anterior–superior spine. To minimize the risk of these potential complications, a wafer osteotomy may be used to develop a sleeve of tissue involving the sartorial insertion. This sleeve also mobilizes the entirety of the LFCN medially and affords protection throughout the procedure. Furthermore, the wafer osteotomy may be re-fixed to the stable pelvis during closure with simple heavy suture fixation alone, avoiding screw insertion or associated removal. Because only a wafer or bone is taken during the spine osteotomy, more bone is available at the anterior–superior iliac spine for fixation of the mobile fragment after repositioning. In this technical note, we describe the wafer osteotomy technique in further detail.
Questionnaire survey on treatment planning techniques for lung stereotactic body radiotherapy in Japan
Authors: Ueda Yoshihiro , Takakura Toru , Ota Seiichi , Kito Satoshi , Sasaki Koji , Shimizu Hidetoshi , Tatsumi Daisaku , Yano Shinsuke , Nakamura Mitsuhiro 
Published: November 2019

ABSTRACTThis study aimed to obtain details regarding treatment planning techniques for lung stereotactic body radiation therapy (SBRT) employed at each institution in Japan by using a questionnaire survey. An Internet questionnaire survey on SBRT procedures performed in 2016 was conducted by the QA/QC committee of the Japan Society of Medical Physics from April to June 2017. The questionnaire assessed two aspects: the environment for SBRT at each institution and the treatment planning techniques with and without respiratory motion management techniques (RMMT). Of the 309 evaluated responses, 218 institutions had performed SBRT. A total of 186 institutions performed SBRT without RMMT and 139 institutions performed SBRT with RMMT. When respiratory motion was ≥10 mm, 69 institutions applied RMMT. The leading RMMT were breath holding (77 institutions), respiratory gating (49 institutions) and real-time tumor tracking (11 institutions). The most frequently used irradiation technique was 3D conformal radiotherapy, which was used in 145 institutions without RMMT and 119 institutions with RMMT. Computed tomography (CT) images acquired under free breathing were mostly used for dose calculation for patients treated without RMMT. The usage ratio of IMRT/VMAT to SBRT is low in Japan, compared to elsewhere in the world (&lt;20% vs ≥70%). Among the available dose calculation algorithms, superposition convolution was the most frequently used regardless of RMMT; however, 2% of institutions have not yet made heterogeneity corrections. In the prescription setting, about half of the institutions applied point prescriptions. The survey results revealed the most frequently used conditions, which may facilitate standardization of treatment techniques in lung SBRT.
Mapping the dark matter halo of early-type galaxy NGC 2974 through orbit-based models with combined stellar and cold gas kinematics
Authors: Yang Meng , Zhu Ling , Weijmans Anne-Marie , van de Ven Glenn , Boardman Nicholas , Morganti Raffaella , Oosterloo Tom 
Published: November 2019

ABSTRACT
We present an orbit-based method of combining stellar and cold gas kinematics to constrain the dark matter profile of early-type galaxies. We apply this method to early-type galaxy NGC 2974, using Pan-STARRS imaging and SAURON stellar kinematics to model the stellar orbits, and introducing H i kinematics from VLA observation as a tracer of the gravitational potential. The introduction of the cold gas kinematics shows a significant effect on the confidence limits of especially the dark halo properties: we exclude more than $95{{\ \rm per\ cent}}$ of models within the 1σ confidence level of Schwarzschild modelling with only stellar kinematics, and reduce the relative uncertainty of the dark matter fraction significantly to $10{{\ \rm per\ cent}}$ within 5Re. Adopting a generalized Navarro–Frenk–White (NFW) dark matter profile, we measure a shallow cuspy inner slope of $0.6^{+0.2}_{-0.3}$ when including the cold gas kinematics in our model. We cannot constrain the inner slope with the stellar kinematics alone.
The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA
Authors: Pinto Rita , Vågbø Cathrine B , Jakobsson Magnus E , Kim Yeji , Baltissen Marijke P , O’Donohue Marie-Françoise , Guzmán Ulises H , Małecki Jędrzej M , Wu Jie , Kirpekar Finn , Olsen Jesper V , Gleizes Pierre-Emmanuel , Vermeulen Michiel , Leidel Sebastian A , Slupphaug Geir , Falnes Pål Ø 
Published: November 2019

Abstract
RNA methylations are essential both for RNA structure and function, and are introduced by a number of distinct methyltransferases (MTases). In recent years, N6-methyladenosine (m6A) modification of eukaryotic mRNA has been subject to intense studies, and it has been demonstrated that m6A is a reversible modification that regulates several aspects of mRNA function. However, m6A is also found in other RNAs, such as mammalian 18S and 28S ribosomal RNAs (rRNAs), but the responsible MTases have remained elusive. 28S rRNA carries a single m6A modification, found at position A4220 (alternatively referred to as A4190) within a stem–loop structure, and here we show that the MTase ZCCHC4 is the enzyme responsible for introducing this modification. Accordingly, we found that ZCCHC4 localises to nucleoli, the site of ribosome assembly, and that proteins involved in RNA metabolism are overrepresented in the ZCCHC4 interactome. Interestingly, the absence of m6A4220 perturbs codon-specific translation dynamics and shifts gene expression at the translational level. In summary, we establish ZCCHC4 as the enzyme responsible for m6A modification of human 28S rRNA, and demonstrate its functional significance in mRNA translation.
Neonatal coning secondary to hypoxic ischaemic encephalopathy: A case study and literature review
Authors: Soliman Yasser , Yusuf Kamran , Blayney Marc , El Shahed Amr I , Belik Jaques 
Published: November 2019

AbstractIntroductionBrain herniation is an extremely rare complication of hypoxic ischaemic encephalopathy (HIE) in the neonatal period with only a single report described. We report a 2-day-old term infant with severe HIE, who developed diffuse brain oedema and herniation.Case presentation and descriptionA term female infant delivered by vacuum, required therapeutic hypothermia for severe encephalopathy. At 36 hours of age, a marked change in neurological status was noted with signs of brainstem involvement. A head Computed Tomography Scan showed uncal and tonsillar herniation.ConclusionVigilance in monitoring neonatal neurological status during therapeutic hypothermia is imperative for early brain herniation detection.
Enhancing control of cell-free metabolism through pH modulation
Authors: Karim Ashty S , Rasor Blake J , Jewett Michael C 
Published: November 2019

Abstract
Engineering metabolism for the synthesis of bio-based products in non-model organisms can be challenging. One specific challenge is that biosynthetic pathways are often built from enzyme candidates sourced from diverse organisms, which can prove difficult to implement in recombinant hosts due to differences in their cellular environments (e.g. pH, cofactor balance). To address this problem, we report a cell-free synthetic biology approach for understanding metabolism in a range of environmental conditions, specifically under varied pH. The key idea is to control the pH of Escherichia coli-based cell-free systems for assessing pathway performance using enzymes sourced from organisms other than E. coli. As a model, we apply this approach to study the impact of pH on the n-butanol biosynthesis pathway derived from clostridia in E. coli lysates. Specifically, we exploit the open, cell-free reaction environment to explore pH outside the habitable range of E. coli, revealing insights into how chemical context impacts the interaction between native metabolism and heterologous enzymes. We find that the pH optimum for butanol production from acetyl-CoA is substantially lower than the optimal pH of glycolysis in E. coli-based crude lysates. In addition, pH is an essential factor to consider when activating metabolic pathways in the cell-free environment due to its effect on reaction yield or enzyme activity, the latter of which is demonstrated in this work for alcohol dehydrogenases from a range of extremophiles. Ultimately, altering metabolism through pH control will allow cell-free systems to be used in studying the metabolic state of organisms and identify suitable enzymes for pathway engineering.
The law applicable to third-party effects of assignments of claims: the UN Convention and the EU Commission Proposal compared
Authors: Bazinas Spyridon V 
Published: November 2019

Abstract
In October 2019, the U.S. ratified the United Nations Convention on the Assignment of Receivables in International Trade (the “Convention”) by the US, thus creating a new impetus for the broad adoption and entry into force of the Convention and with that for the facilitation of international receivables finance. In March 2018, the E.U. Commission issued a Proposal for a Regulation of the European Parliament and of the Council on the law applicable to the third-party effects of assignments of claims (the “Commission Proposal” or “Proposal”). The Commission Proposal includes a first draft of the proposed Regulation (the “draft Regulation”). An alignment of the main rule of the draft Regulation with the equivalent rule in the Convention could result in an internationally uniform conflict-of-laws rule on this matter, which would remove the legal divergences existing among legal systems and reduce the uncertainty as to the law applicable to the third-party effects of assignments of claims. The purpose of this article is to compare the relevant rules of the Convention and the draft Regulation, determine whether this coordinated approach is achieved and, if not, make suggestions as to how it can be achieved to the benefit of all parties involved in international receivables finance.
Improving Access to Safe Anesthetic Care in Rural and Remote Communities in Affluent Countries
Authors: Orser B.A. , Wilson C.R. , Rotstein A.J. , Iglesias S.J. , Spain B.T. , Ranganathan P. , MacDonald W.A. , Ng V. , O’Leary S. , Lafontaine A. 
Published: November 2019

(Anesth Analg. 2019;129(1):294–300)
Low-income and middle-income countries have historically struggled to provide access to anesthesia and surgical services for their patient populations, but this is also a difficulty for the rural areas of higher-income countries such as Australia, Canada, and the United States. The World Health Organization considers anesthesia and surgical services to be part of patients’ rights to health, but it is more difficult for surgical patients to access needed care in rural areas due to the limited availability of medical professionals in those areas. A study of the proposed solutions to these issues can be beneficial not only for Australia, Canada, and the United States, but can also help provide a framework for other countries to improve their population’s access to needed medical care.
New Antibiotic for Community-Acquired Bacterial Pneumonia
Authors: Aschenbrenner Diane S. 
Published: November 2019

Lefamulin (Xenleta) is a new antibiotic approved to treat adults with community-acquired bacterial pneumonia.Lefamulin's labeling warns of the risk of QT interval prolongation, the potential for fetal harm, and the risk of Clostridium difficile–associated diarrhea.
A Kangaroo Care Pathway for NICU Staff and Families
Authors: Stadd Karen , Diehl Beth , Yenokyan Gayane , Aucott Susan W. 
Published: November 2019

Background:Kangaroo care (KC) improves bonding and neonatal health outcomes worldwide. However, concerns for patient safety, interrupted workflow, and parent readiness continued to impede KC in a level IV neonatal intensive care unit (NICU). Its current policy did not recommend using more than 1 staff member during patient transfer. In addition, NICU staff and parents lacked skills training and education regarding the feasibility of routine KC.Purpose:A KC pathway was developed and integrated within a multifaceted, champion-based, simulated educational training program for NICU staff and families to promote earlier and more frequent KC by increasing their knowledge and comfort with this practice.Methods:Patient data collected before and after the study determined the frequency, timing, and mode of respiratory support during KC. Pre- and posttest surveys evaluated nurses' knowledge and comfort level with KC.Results:The frequency of KC occurred 2.4 times more after the intervention. The percentage of KC episodes for intubated patients nearly doubled. The posttest survey scores for nursing knowledge and comfort level also markedly improved.Implications for Practice:The KC pathway ameliorated feelings of discomfort by depicting criteria and instructions for safe practice. Multidisciplinary champions were invaluable in assisting the nursing staff with patient transfer during KC.Implications for Research:More dose–response studies are needed to maximize the clinical benefits of KC in developed countries.
Team-Based Implementation of an Exclusive Human Milk Diet
Authors: Delaney Manthe Eva , Perks Patti H. , Swanson Jonathan R. 
Published: November 2019

Background:
The University of Virginia neonatal intensive care unit is a 51-bed unit with approximately 600 to 700 admissions per year. Despite evidenced-based clinical care, necrotizing enterocolitis (NEC) and feeding intolerance remained problematic.

Purpose:
In September 2016, the neonatal intensive care unit implemented an exclusive human milk diet (EHMD) for infants born 1250 g or less with the goal of reducing NEC, feeding intolerance, parenteral nutrition use, and late-onset sepsis. Length of stay, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity were also evaluated.

Methods:
A work group developed systems for charging and documenting products used in an EHMD. Outcomes were compared with a control group of similar infants born prior to the availability of the EHMD.

Results:
Infants who received an EHMD had significantly fewer late-onset sepsis evaluations (P = .0027) and less BPD (P = .018). While not statistically significant, less surgical NEC was also demonstrated (4 cases vs 1 case, which was 57% of total NEC cases vs 14.3%) while maintaining desirable weight gain and meeting financial goals.

Implications for Practice:
A multidisciplinary team that implements financial and documentation systems can provide a sustainable clinical practice that improves patient outcomes. Ongoing evaluations of clinical and financial data provide valuable information to guide future clinical practices related to the EHMD.

Implications for Research:
Future research on the anti-inflammatory effect of an EHMD is needed to provide direction regarding a potential dose-dependent response for reduced BPD rates and severity. The role of human milk and prevention or mitigation of sepsis is not fully understood, but the reduction of the number of late-onset sepsis evaluations may support the relationship between an EHMD and infection protection. Exploring clinical and financial outcomes for implementing the EHMD in infants born more than 1250 g remains a key area for research.
Robustness of NHANES Estimates of the US Prevalence of a Positive Tuberculin Skin Test
Authors: Haddad Maryam B. , Lash Timothy L. , Hill Andrew N. , Navin Thomas R. , Castro Kenneth G. , Gandhi Neel R. , Winston Carla A. 
Published: November 2019

Background:
A single 2-year National Health and Nutrition Examination Survey (NHANES) cycle is designed to provide accurate and stable estimates of conditions with prevalence of at least 10%. Recent NHANES-based estimates of a tuberculin skin test (TST) ≥10 mm in the noninstitutionalized US civilian population are at most 6.3%.

Methods:
NHANES included a TST in 1971–1972, 1999–2000, and 2011–2012. We examined the robustness of NHANES-based estimates of the US population prevalence of a skin test ≥10 mm with a bias analysis that considered the influence of non-US birth distributions and within-household skin test results, reclassified borderline-positive results, and adjusted for TST item nonresponse.

Results:
The weighted non-US birth distribution among NHANES participants was similar to that in the overall US population; further adjustment was unnecessary. We found no evidence of bias due to sampling multiple participants per household. Prevalence estimates changed 0.3% with reclassification of borderline-positive TST results and 0.2%–0.3% with adjustment for item nonresponse.

Conclusions:
For estimating the national prevalence of a TST ≥10 mm during these three survey cycles, a conventional NHANES analysis using the standard participant weights and masked design parameters that are provided in the public-use datasets appears robust. See video abstract at, http://links.lww.com/EDE/B636.
No difference in medication regimes and dosing in study participants with and without blood pressure control: longitudinal data of the population-based Heinz Nixdorf Recall Study
Authors: Brandt Isabelle , Puth Marie-Therese , Kersting Christine , Moebus Susanne , Erbel Raimund , Jöckel Karl-Heinz , Weltermann Birgitta 
Published: November 2019

Background:
To achieve blood pressure (BP) control adequate dosing of first-line antihypertensive medications is recommended in addition to life-style changes. Given observations that dosing of antihypertensive agents is frequently insufficient, we compared the changes of BP control rates and antihypertensive drug regimens in a prospective German population using a new strategy to analyze medication dosing.

Methods:
This analysis is based on data of the baseline (2000–2003) and the first follow-up examination (2005–2008) of the population-based Heinz Nixdorf Recall study. Participants with hypertension at baseline (BP ≥140/90 mmHg or at least one antihypertensive agent) who participated in both examinations were included.

Results:
Of the 4157 participants, 2289 (55.1%) had hypertension at baseline. The prevalence of participants on antihypertensive agents was 60.3% at baseline and increased to 75.1% at follow-up. The mean number of antihypertensive agents was 2 [±1 SD (standard deviation)] initially and at follow-up. The prevalence of medication-controlled BP did not improve over time (baseline: 54.5%, follow-up: 56.5%). When stratifying by medication-controlled BP, the medication dosing rate slightly increased over time without differences between groups [controlled versus uncontrolled BP: 40.9 versus 46.2% (baseline); 50.1 versus 51.9% (follow-up)].

Conclusion:
Although the prevalence of antihypertensive medication use increased in the study period, the BP control rate did not. In contrast to clinical reasoning, participants with uncontrolled BP did neither receive more agents nor higher dosing despite outcome-relevant hypertension. Our approach to analyze medication dosing suggests a potential to improve cardiovascular outcomes by increasing dosages of antihypertensive agents.