bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shared Cared for Stable Glaucoma Patients: Economic Benefits and Patient-centered Outcomes of a Feasibility Trial
Authors: Goh David , de Korne Dirk F. , Ho Henrietta , Mathur Ranjana , Chakraborty Bibhas , Van Hai Nguyen , Wai Charity , Perera Shamira , Aung Tin , Wong Tien Y. , Lamoureux Ecosse L. 
Published: December 2017

Purpose:The purpose of this article is to assess the quality of care and economic benefits of a shared care model managing patients with stable glaucoma in a primary eye care (PEC) clinic compared with a tertiary specialist outpatient clinic (SOC) in Singapore.Patients and Methods:A randomized equivalence feasibility trial was preformed comparing the PEC with SOC models. Participants recruited from the SOC had no visual field progression or change in management for at least 3 years, were on a maximum of a single glaucoma medication, had no previous tube-shunt implant and were at least 3-year posttrabeculectomy surgery.Primary outcomes were clinical assessment and management, economic benefits, and patient satisfaction. Differences were analyzed using equivalence testing and generalized odds ratios.Results:The trial included 233 patients, consisting of 42.1% glaucoma disc suspects (PEC: 47.4%; SOC: 36.8%), 27.5% primary angle closure suspects (PEC: 25.0%; SOC: 29.9%), 13.7% with ocular hypertension (PEC: 13.8%; SOC: 13.7%), 3.9% with primary angle closure glaucoma (PEC: 4.3%; SOC: 3.4%), and 3.0% with primary open angle glaucoma (PEC: 1.7%; SOC: 4.3%). Glaucoma clinical care for patients at PEC was as good as SOC [rate difference, 6.83%; 95% confidence interval (CI), 2.84-11.12) and management (rate difference, 7.69%; 95% CI, 3.21-12.17). In 23 cases (9.9%), 5.2% at PEC and 14.5% at SOC, there was disconcordance with the gold standard of senior consultant. Patient satisfaction at the PEC was equally high when compared with SOC (generalized odds ratio, 1.43; CI, 0.50-2.00). Direct costs per patient visit were 43% lower at PEC compared with SOC.Conclusion:Managing stable glaucoma patients at a primary care setting is a cost saving, safe, and effective shared care while enhancing professional collaboration between hospital and community settings.
A 20-Year Experience with 202 Segmental Mandibulectomy Defects: A Defect Classification System, Algorithm for Flap Selection, and Surgical Outcomes
Authors: Cordeiro Peter G. , Henderson Peter W. , Matros Evan 
Published: December 2017

Background:
This study establishes a novel and broadly applicable defect classification system and flap selection algorithm for segmental mandibulectomy defects that emphasize the importance of the soft-tissue deficit, in addition to that of the bony defect.

Methods:
Between 1992 and 2011, 202 patients with mandibulectomy defects underwent immediate reconstruction performed by a single surgeon. Details of the bony and soft-tissue defects, recommendations for the most appropriate reconstruction for each clinical scenario, and surgical outcomes are presented.

Results:
A total of 211 flaps were performed in 202 patients. Forty-one (19 percent) were nonosseous only, and 170 (81 percent) were osseous-containing. The majority of osseous flaps were fibula osseous or osteocutaneous flaps (91 percent), and the majority of nonosseous flaps were vertical rectus abdominis myocutaneous flaps (68 percent). Flap selection was influenced by the number of soft-tissue zones resected; defects of one soft-tissue zone or less were predominantly reconstructed with an osseous flap, whereas defects that involved four or more zones underwent reconstruction with only a soft-tissue flap in 55 percent of cases.

Conclusions:
The algorithm for reconstruction of the mandibulectomy defect must include both nonosseous and osseous flaps based on defect size, location, and number of soft-tissue zones involved. As the extent of the soft-tissue defect increases, nonosseous flaps are preferred because of greater reliability of the skin island. The surgical outcomes associated with this algorithm are similar to or better than what is published in the literature. This series represents the largest reported single-surgeon experience with mandibulectomy defect reconstruction.
Discovery and biosynthesis of the antibiotic bicyclomycin in distant bacterial classes
Authors: Vior Natalia M. , Lacret Rodney , Chandra Govind , Dorai-Raj Siobhán , Trick Martin , Truman Andrew W. 
Published: December 2017

ABSTRACTBicyclomycin (BCM) is a clinically promising antibiotic that is biosynthesised byStreptomyces cinnamoneusDSM 41675. BCM is structurally characterized by a core cyclo(L-Ile-L-Leu) 2,5-diketopiperazine (DKP) that is extensively oxidized. Here, we identify the BCM biosynthetic gene cluster, which shows that the core of BCM is biosynthesised by a cyclodipeptide synthase and the oxidative modifications are introduced by five 2-oxoglutarate-dependent dioxygenases and one cytochrome P450 monooxygenase. The discovery of the gene cluster enabled the identification of BCM pathways encoded in the genomes of hundreds ofPseudomonas aeruginosaisolates distributed globally, and heterologous expression of the pathway fromP. aeruginosaSCV20265 demonstrated that the product is chemically identical to BCM produced byS. cinnamoneus. Overall, putative BCM gene clusters have been found in at least seven genera spanningActinobacteriaandProteobacteria(Alpha-, Beta-andGamma-). This represents a rare example of horizontal gene transfer of an intact biosynthetic gene cluster across such distantly related bacteria, and we show that these gene clusters are almost always associated with mobile genetic elements.IMPORTANCEBicyclomycin is the only natural product antibiotic that selectively inhibits the transcription termination factor Rho. This mechanism of action, combined with its proven biological safety and its activity against clinically relevant Gram-negative bacterial pathogens, makes it a very promising antibiotic candidate. Here, we report the identification of the bicyclomycin biosynthetic gene cluster in the known producing organismStreptomyces cinnamoneus, which will enable the engineered production of new bicyclomycin derivatives. The identification of this gene cluster also led to the discovery of hundreds of bicyclomycin pathways encoded in highly diverse bacteria, including the opportunistic pathogenPseudomonas aeruginosa. This wide distribution of a complex biosynthetic pathway is very unusual, and provides an insight into how a pathway for an antibiotic can be transferred between diverse bacteria.
An interactive programming paradigm for realtime experimentation with remote living matter
Authors: Washington Peter , Samuel-Gama Karina G. , Goyal Shirish , Ramaswami Ashwin , Riedel-Kruse Ingmar H. 
Published: December 2017

Recent advancements in life-science instrumentation and automation enable entirely new modes of human interaction with microbiological processes and corresponding applications for science and education through biology cloud labs. A critical barrier for remote life-science experimentation is the absence of suitable abstractions and interfaces for programming living matter. To this end we conceptualize a programming paradigm that provides stimulus control functions and sensor control functions for realtime manipulation of biological (physical) matter. Additionally, a simulation mode facilitates higher user throughput, program debugging, and biophysical modeling. To evaluate this paradigm, we implemented a JavaScript-based web toolkit, ‘Bioty’, that supports realtime interaction with swarms of phototactic Euglena cells hosted on a cloud lab. Studies with remote users demonstrate that individuals with little to no biology knowledge and intermediate programming knowledge were able to successfully create and use scientific applications and games. This work informs the design of programming environments for controlling living matter in general and lowers the access barriers to biology experimentation for professional and citizen scientists, learners, and the lay public.Significance StatementBiology cloud labs are an emerging approach to lower access barriers to life-science experimentation. However, suitable programming approaches and user interfaces are lacking, especially ones that enable the interaction with the living matter itself - not just the control of equipment. Here we present and implement a corresponding programming paradigm for realtime interactive applications with remotely housed biological systems, and which is accessible and useful for scientists, programmers and lay people alike. Our user studies show that scientists and non-scientists are able to rapidly develop a variety of applications, such as interactive biophysics experiments and games. This paradigm has the potential to make first-hand experiences with biology accessible to all of society and to accelerate the rate of scientific discovery.
Control of meiotic double-strand-break formation by ATM: local and global views
Authors: Lukaszewicz Agnieszka , Lange Julian , Keeney Scott , Jasin Maria 
Published: December 2017

ABSTRACTDNA double-strand breaks (DSBs) generated by the SPO11 protein initiate meiotic recombination, an essential process for successful chromosome segregation during gametogenesis. The activity of SPO11 is controlled by multiple factors and regulatory mechanisms, such that the number of DSBs is limited and DSBs form at distinct positions in the genome and at the right time. Loss of this control can affect genome integrity or cause meiotic arrest by mechanisms that are not fully understood. Here we focus on the DSB-responsive kinase ATM and its functions in regulating meiotic DSB numbers and distribution. We review the recently discovered roles of ATM in this context, discuss their evolutionary conservation, and examine future research perspectives.
Robust expression variability testing reveals heterogeneous T cell responses
Authors: Eling Nils , Richard Arianne C. , Richardson Sylvia , Marioni John C. , Vallejos Catalina A. 
Published: December 2017

SummaryCell-to-cell transcriptional variability in otherwise homogeneous cell populations plays a crucial role in tissue function and development. Single-cell RNA sequencing can characterise this variability in a transcriptome-wide manner. However, technical variation and the confounding between variability and mean expression estimates hinders meaningful comparison of expression variability between cell populations. To address this problem, we introduce a novel analysis approach that extends the BASiCS statistical framework to derive a residual measure of variability that is not confounded by mean expression. Moreover, we introduce a new and robust procedure for quantifying technical noise in experiments where technical spike-in molecules are not available. We illustrate how our method provides biological insight into the dynamics of cell-to-cell expression variability, highlighting a synchronisation of the translational machinery in immune cells upon activation. Additionally, our approach identifies new patterns of variability across CD4+ T cell differentiation.
A single-cell catalogue of regulatory states in the ageing Drosophila brain
Authors: Davie Kristofer , Janssens Jasper , Koldere Duygu , Pech Uli , Aibar Sara , De Waegeneer Maxime , Makhzami Samira , Christiaens Valerie , González-Blas Carmen Bravo , Hulselmans Gert , Spanier Katina I. , Moerman Thomas , Vanspauwen Bram , Lammertyn Jeroen , Thienpont Bernard , Liu Sha , Verstreken Patrik , Aerts Stein 
Published: December 2017

SummaryThe diversity of cell types and regulatory states in the brain, and how these change during ageing, remains largely unknown. Here, we present a single-cell transcriptome catalogue of the entire adult Drosophila melanogaster brain sampled across its lifespan. Both neurons and glia age through a process of “regulatory erosion”, characterized by a strong decline of RNA content, and accompanied by increasing transcriptional and chromatin noise. We identify more than 50 cell types by specific transcription factors and their downstream gene regulatory networks. In addition to neurotransmitter types and neuroblast lineages, we find a novel neuronal cell state driven by datilografo and prospero. This state relates to neuronal birth order, the metabolic profile, and the activity of a neuron. Our single-cell brain catalogue reveals extensive regulatory heterogeneity linked to ageing and brain function and will serve as a reference for future studies of genetic variation and disease mutations.
Cell “hashing” with barcoded antibodies enables multiplexing and doublet detection for single cell genomics
Authors: Stoeckius Marlon , Zheng Shiwei , Houck-Loomis Brian , Hao Stephanie , Yeung Bertrand Z. , Smibert Peter , Satija Rahul 
Published: December 2017

ABSTRACTDespite rapid developments in single cell sequencing technology, sample-specific batch effects, detection of cell doublets, and the cost of generating massive datasets remain outstanding challenges. Here, we introduce cell “hashing”, where oligo-tagged antibodies against ubiquitously expressed surface proteins are used to uniquely label cells from distinct samples, which can be subsequently pooled. By sequencing these tags alongside the cellular transcriptome, we can assign each cell to its sample of origin, and robustly identify doublets originating from multiple samples. We demonstrate our approach by pooling eight human PBMC samples on a single run of the 10x Chromium system, substantially reducing our per-cell costs for library generation. Cell “hashing” is inspired by, and complementary to, elegant multiplexing strategies based on genetic variation, which we also leverage to validate our results. We therefore envision that our approach will help to generalize the benefits of single cell multiplexing to diverse samples and experimental designs.
A Testis ER Chaperone Marks Mature Olfactory and Vomeronasal Sensory Neurons
Authors: Dalton Ryan P 
Published: December 2017

AbstractThe proper folding of most secreted and membrane proteins involves interaction with endoplasmic reticulum-resident, glycan-binding chaperones. Some of these chaperones, such as Calreticulin and Calnexin, are nearly ubiquitous, while others are found only in specific cell types, presumably reflecting a role in biosynthesis of proteins specific to those cells. Herein, I have identified Calmegin (Clgn), a chaperone required for fertile spermatogenesis, as a marker of mature neurons in the olfactory system. CLGN was expressed by olfactory marker protein (OMP)-positive neurons in both the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). CLGN was detected both in the perinuclear ER network and in axons. Finally expression of Atf5, a transcription factor required for OSN and VSN development, was both required and sufficient for robust CLGN expression in OSNs and VSNs. Together these findings establish that an ER chaperone required for sperm fertility is developmentally regulated in olfactory neurons, provide a novel marker of mature olfactory neurons, and suggest common mechanisms of secretory protein biogenesis in these cell types.
Cellular diversity in theDrosophilamidbrain revealed by single-cell transcriptomics
Authors: Croset Vincent , Treiber Christoph D , Waddell Scott 
Published: December 2017

AbstractTo understand the brain, molecular details need to be overlaid onto neural wiring diagrams so that synaptic mode, neuromodulation and critical signaling operations can be considered. Single-cell transcriptomics provide a unique opportunity to collect this information. Here we present an initial analysis of thousands of individual cells fromDrosophilamidbrain, that were acquired using Drop-Seq. A number of approaches permitted the assignment of transcriptional profiles to several major brain regions and cell-types. Expression of biosynthetic enzymes and reuptake mechanisms allows all the neurons to be typed according to the neurotransmitter or neuromodulator that they produce and presumably release. Some neuropeptides are preferentially co-expressed in neurons using a particular fast-acting transmitter, or monoamine. Neuromodulatory and neurotransmitter receptor subunit expression illustrates the potential of these molecules in generating complexity in neural circuit function. This cell atlas dataset provides an important resource to link molecular operations to brain regions and complex neural processes.
Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats
Authors: Hu Min , Zhang Yuehui , Feng Jiaxing , Xu Xue , Zhang Jiao , Zhao Wei , Guo Xiaozhu , Li Juan , Vestin Edvin , Cui Peng , Li Xin , Wu Xiao-ke , Brännström Mats , Shao Linus R , Billig Håkan 
Published: December 2017

AbstractImpaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.
Analysing the impact of different classical controller strategies on the dynamics performance of production-inventory systems using state space approach
Authors: AL-Khazraji Huthaifa , Cole Colin , Guo William 
Published: December 2017

Purpose
The purpose of this paper is to examine the impact of applying two classical controller strategies, including two proportional (P) controllers with two feedback loops and one proportional–integral–derivative (PID) controller with one feedback loop, on the order and inventory performance within a production-inventory control system.

Design/methodology/approach
The simulation experiments of the dynamics behaviour of the production-inventory control system are conducted using a model based on control theory techniques. The Laplace transformation of an Order–Up–To (OUT) model is obtained using a state-space approach, and then the state-space representation is used to design and simulate a controlled model. The simulations of each model with two control configurations are tested by subjecting the system to a random retail sales pattern. The performance of inventory level is quantified by using the Integral of Absolute Error (IAE), whereas the bullwhip effect is measured by using the Variance ratio (Var).

Findings
The simulation results show that one PID controller with one feedback loop outperforms two P controllers with two feedback loops at reducing the bullwhip effect and regulating the inventory level.

Originality/value
The production-inventory control system is broken down into three components, namely: the forecasting mechanism, controller strategy and production-inventory process. A state-space approach is adopted to design and simulate the different controller strategy.
Employment Effects of the CAP in Italian Agriculture: Territorial Diversity and Policy Effectiveness
Authors: Mantino Francesco 
Published: December 2017

SummaryThe objectives of this article are to provide insights on the employment impacts of CAP measures in Italian agriculture over the period 2007–14, and to explore the diversity of these impacts in four types of area. The main policy tools of the First Pillar have debatable impacts on agricultural employment in all area types, although they were not specifically designed to create jobs but to ensure food production and socio‐environmentally sustainable land management practices. Second Pillar measures bring positive and significant rural development effects to the areas of Italy studied, but these effects differ according to the type of measure: farm and agro‐industrial investment support generates higher employment effects than measures for the agri‐environment, less favoured areas, or rural diversification. The intensity of these effects is higher in those areas where conditions for development are more favourable. They still have positive effects in Peripheral Areas, but the cost of creating new jobs in such areas is higher. It can be argued that we need a more flexible CAP, capable of fitting diverse territorial needs, and strengthened by rules of policy design and implementation more oriented towards the pursuit of territorial cohesion.
Material Needs of Emergency Department Patients: A Systematic Review
Authors: Malecha Patrick W. , Williams James H. , Kunzler Nathan M. , Goldfrank Lewis R. , Alter Harrison J. , Doran Kelly M. 
Published: December 2017

AbstractBackgroundInterest in social determinants of health (SDOH) has expanded in recent years, driven by a recognition that such factors may influence health outcomes, services use, and health care costs. One subset of SDOH is material needs such as housing and food. We conducted a systematic review of the literature on material needs among emergency department (ED) patients in the United States.MethodsWe followed PRISMA guidelines for systematic review methodology. With the assistance of a research librarian, four databases were searched for studies examining material needs among ED patients. Two reviewers independently screened titles, abstracts, and full text to identify eligible articles. Information was abstracted systematically from eligible articles.ResultsForty‐three articles were eligible for inclusion. There was heterogeneity in study methods; single‐center, cross‐sectional studies were most common. Specific material needs examined included homelessness, poverty, housing insecurity, housing quality, food insecurity, unemployment, difficulty paying for health care, and difficulty affording basic expenses. Studies overwhelmingly supported the notion that ED patients have a high prevalence of a number of material needs.ConclusionsDespite some limitations in the individual studies examined in this review, the plurality of prior research confirms that the ED serves a vulnerable population with high rates of material needs. Future research is needed to better understand the role these needs play for ED patients and how to best address them.
Dielectric relaxation induced internal electric field and its effect on magnetoelectric state in Co4Nb2O9
Authors: Xie Yuanmiao , Zang Hao , Ceng Wen‐Dan , Wang Shuting , Wang Chunchang 
Published: December 2017

AbstractPyrocurrent and dielectric properties of magnetoelectric antiferromagnet Co4Nb2O9 have been investigated. The sample shows 2 thermally activated dielectric relaxations in the temperature range far above Néel temperature with the low‐ and high‐temperature ones being a dipolar and Maxwell‐Wagner relaxations, respectively. Two types of dipoles: relaxing dipoles and magnetic‐field‐induced dipoles were found in the sample. An internal electric field is formed due to the ordering of relaxing dipoles. Three current peaks were observed. The 2 higher temperature current peaks correspond to the dielectric relaxations. The lowest temperature current peak contains a positive tip and negative dip. The tip and dip are related to the depolarization of ferroelectricity induced by external and internal fields, respectively.