bluuebunny/crossref_metadata_2025 huggingface dataset:
Implications of region‐specific gene expression for development of the partially fused petunia corolla
Authors: Preston Jill C. , Powers Beck , Kostyun Jamie L. , Driscoll Heather , Zhang Fan , Zhong Jinshun
Published: June 2019

Angiosperm petal fusion (sympetaly) has evolved multiple times independently and is associated with increased specificity between plants and their pollinators. To uncover developmental genetic changes that might have led to the evolution of sympetaly in the asterid core eudicot genus Petunia (Solanaceae), we carried out global and fine‐scale gene expression analyses in different regions of the corolla. We found that, despite several similarities with the choripetalous model species Arabidopsis thaliana in the proximal–distal transcriptome, the Petunia axillaris fused and proximal corolla tube expresses several genes that in A. thaliana are associated with the distal petal region. This difference aligns with variation in petal shape and fusion across ontogeny of the two species. Moreover, differential gene expression between the unfused lobes and fused tube of P. axillaris petals revealed three strong candidate genes for sympetaly based on functional annotation in organ boundary specification. Partial silencing of one of these, the HANABA TARANU (HAN)‐like gene PhGATA19, resulted in reduced fusion of Petunia hybrida petals, with silencing of both PhGATA19 and its close paralog causing premature plant senescence. Finally, detailed expression analyses for the previously characterized organ boundary gene candidate NO APICAL MERISTEM (NAM) supports the hypothesis that it establishes boundaries between most P. axillaris floral organs, with the exception of boundaries between petals.
Leader–Follower Consensus Control of Multiple Quadcopters Under Communication Delays
Authors: Huang Zipeng , Pan Ya-Jun , Bauer Robert
Published: June 2019

This paper develops a novel decentralized leader–follower consensus algorithm for multiple-quadcopter systems under uniform constant and asynchronous time-varying communication delays. The consensus problem is formulated as the stability analysis and static controller design problem of a delayed system by defining the consensus error dynamics. Lyapunov-based methods along with the linear matrix inequality (LMI) techniques are utilized to derive the sufficient conditions for the control gain design that ensure asymptotic consensusability in the constant delay case, and consensus with bounded errors in the time-varying delay case. Also the computational complexity of solving control gains can be significantly reduced by decomposing the sufficient conditions into a set of equivalent low-dimensional conditions under undirected communication topologies. Simulation results show that larger systems are generally more susceptible to communication delays, and systems are more robust to delays when more followers are directly connected to the leader.
Hard Italian cheese, by near-ambient pressure XPS
Authors: Roychowdhury Tuhin , Bahr Stephan , Dietrich Paul , Meyer Michael , Thißen Andreas , Linford Matthew R.
Published: June 2019

In this submission, we show survey, O 1s, and C 1s near ambient pressure x-ray photoelectron spectroscopy (NAP-XPS) spectra from a hard Italian cheese, a material that could not be analyzed by conventional approaches without special sample preparation. The C 1s spectrum is fit under the assumption that the surface of the cheese is primarily fat (triglyceride), which is expected to be the lowest free energy component of the material. The O 1s envelope corresponding to the cheese was well fit to two components of equal area.
Tenofovir Plasma Concentration from Preexposure Prophylaxis at the Time of Potential HIV Exposure: a Population Pharmacokinetic Modeling and Simulation Study Involving Serodiscordant Couples in East Africa
Authors: Mallayasamy Surulivelrajan , Chaturvedula Ayyappa , Fossler Michael J. , Sale Mark , Goti Vineet , Bumpus Namandje N. , Marzinke Mark A. , Hendrix Craig W. , Haberer Jessica E. ,   for the Partners Demonstration Project Team, Baeten Jared , Celum Connie , Heffron Renee , Donnell Deborah , Barnabas Ruanne , Haberer Jessica , Haugen Harald , Hendrix Craig , Kidoguchi Lara , Marzinke Mark , Morrison Susan , Morton Jennifer , Ware Norma , Wyatt Monique , Asiimwe Stephen , Tindimwebwa Edna , Katabira Elly , Bulya Nulu , Bukusi Elizabeth , Odoyo Josephine , Mugo Nelly Rwamba , Ngure Kenneth
Published: June 2019

The Partners Demonstration Project was a prospective, open-label, implementation science-driven study of preexposure prophylaxis (PrEP) among heterosexual HIV serodiscordant couples in Kenya and Uganda. Adherence data were collected using the Medication Event Monitoring System (MEMS), and time of sexual activity was collected using the mobile phone short message service (SMS). Two plasma samples were collected at a single study visit.
Allosteric Regulation of HIV-1 Capsid Structure for Gag Assembly, Virion Production, and Viral Infectivity by a Disordered Interdomain Linker
Authors: Koma Takaaki , Kotani Osamu , Miyakawa Kei , Ryo Akihide , Yokoyama Masaru , Doi Naoya , Adachi Akio , Sato Hironori , Nomaguchi Masako
Published: June 2019

HIV-1 particle production and infection are highly ordered processes. Viral Gag proteins play a central role in the assembly and disassembly of viral molecules. Of these, capsid protein (CA) is a major contributor to the Gag-Gag interactions. CA consists of two structured domains, i.e., N-terminal (NTD) and C-terminal (CTD) domains, connected by an unstructured domain named the interdomain linker. While multiple regions in the NTD and CTD are reported to play roles in virion morphogenesis and infectivity, the roles of the linker region in Gag assembly and virus particle formation remain elusive. In this study, we showed by biological and molecular analyses that the linker region functions as an intramolecular modulator to tune Gag assembly, virion production, and viral infectivity. Our study thus illustrates a hitherto-unrecognized mechanism, an allosteric regulation of CA structure by the disordered protein element, for HIV-1 replication.
Retrograde Regulation by the Viral Protein Kinase Epigenetically Sustains the Epstein-Barr Virus Latency-to-Lytic Switch To Augment Virus Production
Authors: Li Xiaofan , Kozlov Sergei V. , El-Guindy Ayman , Bhaduri-McIntosh Sumita
Published: June 2019

Herpesviruses infect nearly all humans and persist quiescently for the life of the host. These viruses intermittently activate into the lytic phase to produce infectious virus, thereby causing disease. To ensure that lytic activation is not prematurely terminated, expression of the virally encoded lytic switch protein needs to be sustained. In studying Epstein-Barr virus, one of the most prevalent human herpesviruses that also causes cancer, we have discovered that a viral kinase activated by the viral lytic switch protein partners with a cellular kinase to deactivate a silencer of the lytic switch protein, thereby providing a positive feedback loop to ensure successful completion of the viral productive phase. Our findings highlight key nodes of interaction between the host and virus that could be exploited to treat lytic phase-associated diseases by terminating the lytic phase or kill cancer cells harboring herpesviruses by accelerating the completion of the lytic cascade.
β-Lactam Antibiotics Enhance the Pathogenicity of Methicillin-Resistant Staphylococcus aureus via SarA-Controlled Lipoprotein-Like Cluster Expression
Authors: Shang Weilong , Rao Yifan , Zheng Ying , Yang Yi , Hu Qiwen , Hu Zhen , Yuan Jizhen , Peng Huagang , Xiong Kun , Tan Li , Li Shu , Zhu Junmin , Li Ming , Hu Xiaomei , Mao Xuhu , Rao Xiancai
Published: June 2019

β-Lactam antibiotics are widely applied to treat infectious diseases. However, certain poor disease outcomes caused by β-lactams remain poorly understood. In this study, we have identified a cluster of lipoprotein-like genes (
lpl
,
sa2275
–
sa2273
) that is upregulated in the major clinically prevalent MRSA clones in response to subinhibitory concentrations of β-lactam induction. The major highlight of this work is that β-lactams stimulate the expression of SarA, which directly binds to the
lpl
cluster promoter region and upregulates
lpl
expression in MRSA. Deletion of
lpl
significantly decreases proinflammatory cytokine levels
in vitro
and
in vivo
. The β-lactam-induced Lpls enhance host inflammatory responses by triggering the Toll-like-receptor-2-mediated expressions of interleukin-6 and tumor necrosis factor alpha. The β-lactam-induced Lpls are important virulence factors that enhance MRSA pathogenicity. These data elucidate that subinhibitory concentrations of β-lactams can exacerbate the outcomes of MRSA infection through induction of
lpl
controlled by the global regulator SarA.
Pyruvate Homeostasis as a Determinant of Parasite Growth and Metabolic Plasticity in Toxoplasma gondii
Authors: Xia Ningbo , Ye Shu , Liang Xiaohan , Chen Pu , Zhou Yanqin , Fang Rui , Zhao Junlong , Gupta Nishith , Yang Shuzhen , Yuan Jing , Shen Bang
Published: June 2019

Toxoplasma gondii
infects almost all warm-blooded animals, and metabolic flexibility is deemed critical for its successful parasitism in diverse hosts. Glucose and glutamine are the major carbon sources to support parasite growth. In this study, we found that
Toxoplasma
is also competent in utilizing lactate and alanine and, thus, exhibits exceptional metabolic versatility. Notably, all these nutrients need to be converted to pyruvate to fuel the lytic cycle, and achieving a continued pyruvate supply is vital to parasite survival and metabolic flexibility. Although pyruvate can be generated by two distinct pyruvate kinases, located in cytosol and apicoplast, respectively, the cytosolic enzyme is the main source of subcellular pyruvate, and cooperative usage of pyruvate among multiple organelles is critical for parasite growth and virulence. These findings expand our current understanding of carbon metabolism in
Toxoplasma gondii
and related parasites while providing a basis for designing novel antiparasitic interventions.
The Landscape of Phenotypic and Transcriptional Responses to Ciprofloxacin in Acinetobacter baumannii: Acquired Resistance Alleles Modulate Drug-Induced SOS Response and Prophage Replication
Authors: Geisinger Edward , Vargas-Cuebas Germán , Mortman Nadav J. , Syal Sapna , Dai Yunfei , Wainwright Elizabeth L. , Lazinski David , Wood Stephen , Zhu Zeyu , Anthony Jon , van Opijnen Tim , Isberg Ralph R.
Published: June 2019

Fluoroquinolones have been extremely successful antibiotics due to their ability to target multiple bacterial enzymes critical to DNA replication, the topoisomerases DNA gyrase and topo IV. Unfortunately, mutations lowering drug affinity for both enzymes are now widespread, rendering these drugs ineffective for many pathogens. To undermine this form of resistance, we examined how bacteria with target alterations differentially cope with fluoroquinolone exposures. We studied this problem in the nosocomial pathogen
A. baumannii
, which causes drug-resistant life-threatening infections. Employing genome-wide approaches, we uncovered numerous pathways that could be exploited to raise fluoroquinolone sensitivity independently of target alteration. Remarkably, fluoroquinolone targeting of topo IV in specific mutants caused dramatic hyperinduction of prophage replication and enhanced the mutagenic DNA damage response, but these responses were muted in strains with DNA gyrase as the primary target. This work demonstrates that resistance evolution via target modification can profoundly modulate the antibiotic stress response, revealing potential resistance-associated liabilities.
Metaphenomic Responses of a Native Prairie Soil Microbiome to Moisture Perturbations
Authors: Roy Chowdhury Taniya , Lee Joon-Yong , Bottos Eric M. , Brislawn Colin J. , White Richard Allen , Bramer Lisa M. , Brown Joseph , Zucker Jeremy D. , Kim Young-Mo , Jumpponen Ari , Rice Charles W. , Fansler Sarah J. , Metz Thomas O. , McCue Lee Ann , Callister Stephen J. , Song Hyun-Seob , Jansson Janet K.
Published: June 2019

Climate change is predicted to result in increased drought extent and intensity in the highly productive, former tallgrass prairie region of the continental United States. These soils store large reserves of carbon. The decrease in soil moisture due to drought has largely unknown consequences on soil carbon cycling and other key biogeochemical cycles carried out by soil microbiomes. In this study, we found that soil drying had a significant impact on the structure and function of soil microbial communities, including shifts in expression of specific metabolic pathways, such as those leading toward production of osmoprotectant compounds. This study demonstrates the application of an untargeted multi-omics approach to decipher details of the soil microbial community’s metaphenotypic response to environmental perturbations and should be applicable to studies of other complex microbial systems as well.
The Power of Metabolism for Predicting Microbial Community Dynamics
Authors: Chacón Jeremy M. , Harcombe William R.
Published: June 2019

Quantitative understanding and prediction of microbial community dynamics are an outstanding challenge. We test the hypothesis that metabolic mechanisms provide a foundation for accurate prediction of dynamics in microbial systems. In our research, metabolic models have been able to accurately predict species interactions, evolutionary trajectories, and response to perturbation in simple synthetic consortia.
Toward Autonomous Antibiotic Discovery
Authors: de la Fuente-Nunez Cesar
Published: June 2019

Machines hold the potential to replace humans in many societal endeavors, and drug discovery is no exception. Antibiotic innovation has been stalled for decades, which has coincided with an alarming increase in multidrug-resistant bacteria.
Proteomic Profiling, Transcription Factor Modeling, and Genomics of Evolved Tolerant Strains Elucidate Mechanisms of Vanillin Toxicity in Escherichia coli
Authors: Pattrick Calum A. , Webb Joseph P. , Green Jeffrey , Chaudhuri Roy R. , Collins Mark O. , Kelly David J.
Published: June 2019

A particular problem for the biotechnological production of many of the valuable chemicals that we are now able to manufacture in bacterial cells is that these products often poison the cells producing them. Solutions to improve product yields or alleviate such toxicity using the techniques of modern molecular biology first require a detailed understanding of the mechanisms of product toxicity. Here we have studied the economically important flavor compound vanillin, an aromatic aldehyde that exerts significant toxic effects on bacterial cells. We used high-resolution protein abundance analysis as a starting point to determine which proteins are upregulated and which are downregulated by growth with vanillin, followed by gene expression and mutant studies to understand the mechanism of the response. In a second approach, we evolved bacterial strains with higher vanillin tolerance. Their genome sequences have yielded novel insights into vanillin tolerance that are complementary to the proteomics data set.
Alteration of Proteomes in First-Generation Cultures of Bacillus pumilus Spores Exposed to Outer Space
Authors: Chiang Abby J. , Malli Mohan Ganesh Babu , Singh Nitin K. , Vaishampayan Parag A. , Kalkum Markus , Venkateswaran Kasthuri
Published: June 2019

Spore-forming bacteria are well known for their resistance to harsh environments and are of concern for spreading contamination to extraterrestrial bodies during future life detection missions.
Bacillus pumilus
has been regularly isolated from spacecraft-associated surfaces and exhibited unusual resistance to ultraviolet light and other sterilization techniques. A better understanding of the mechanisms of microbial survival and enhanced resistance is essential for developing novel disinfection protocols for the purpose of planetary protection. While genomic analyses did not reveal the unique characteristics that explain elevated UV resistance of space-exposed
B. pumilus
, the proteomics study presented here provided intriguing insight on key metabolic changes. The observed proteomics aberrations reveal a complex biological phenomenon that plays a role in bacterial survival and adaptation under long-term exposure to outer space. This adaptive ability of microorganisms needs to be considered by those tasked with eliminating forward contamination.
Multi-omics Signature of
Candida auris
, an Emerging and Multidrug-Resistant Pathogen
Authors: Zamith-Miranda Daniel , Heyman Heino M. , Cleare Levi G. , Couvillion Sneha P. , Clair Geremy C. , Bredeweg Erin L. , Gacser Attila , Nimrichter Leonardo , Nakayasu Ernesto S. , Nosanchuk Joshua D.
Published: June 2019

Candida auris
was first described in Japan in 2009 and has now been the cause of significant outbreaks across the globe. The high number of isolates that are resistant to one or more antifungals, as well as the high mortality rates from patients with bloodstream infections, has attracted the attention of the medical mycology, infectious disease, and public health communities to this pathogenic fungus. In the current work, we performed a broad multi-omics approach on two clinical isolates isolated in New York, the most affected area in the United States and found that the omic profile of
C. auris
differs significantly from
C. albicans
. In addition to our insights into
C. auris
carbon utilization and lipid and protein content, we believe that the availability of these data will enhance our ability to combat this rapidly emerging pathogenic yeast.
Debris-flow volume quantile prediction from catchment morphometry
Authors: de Haas Tjalling , Densmore Alexander L.
Published: June 2019

Estimation of the volumes of potential future debris flows is a key factor in hazard assessment and mitigation. Worldwide, however, there are few catchments for which detailed volume-frequency information is available. We (1) reconstructed volume-frequency curves for 10 debris-flow catchments in Saline Valley, California (USA), from a large number of well-preserved, unmodified surficial flow deposits, and (2) assessed the correlations between lobe-volume quantiles and a set of morphometric catchment characteristics. We found statistically significant correlations between lobe-volume quantiles, including median and maximum, and catchment relief, length (planimetric distance from the fan apex to the most distant point along the watershed boundary), perimeter, and Melton ratio (relief divided by the square root of catchment area). These findings show that it may be possible to roughly estimate debris-flow lobe-volume quantiles from basic catchment characteristics that can be obtained from globally available elevation data. This may assist in design-volume estimation for debris-flow catchments where past flow volumes are otherwise unknown.
Late Oligocene–early Miocene transformation of postcollisional magmatism in Tibet
Authors: Guo Zhengfu , Wilson Marjorie
Published: June 2019

Uplift of the Tibetan Plateau is thought to be one of the most important orogenic and climate forcing events of the Cenozoic Era, associated with geodynamic changes related to India-Asia collision and subsequent continental lithosphere subduction. However, the fate and scale of the subducted continental lithosphere segments remain highly controversial. Using a comprehensive compilation of the spatiotemporal distribution of postcollisional magmatic rocks across Tibet, together with new geochemical and Sr-Nd-Pb isotopic data and modeling simulations, we propose a holistic, two-stage evolutionary model to explain the link between genesis of the magmas and continental subduction. The magmatism prior to 25 Ma resulted from continuous upwelling of a carbonate-rich upper-mantle plume induced by northward underthrusting of Indian oceanic and continental lithosphere with its cover of Tethyan platform carbonate sediments, whereas magmatism after 25 Ma was related to opposing north-directed and south-directed continental subduction. Our model indicates a transformation in the distribution and nature of the magmatism in Tibet at ca. 25 Ma, which reflects a significant change in the Himalayan-Tibetan orogen and associated mantle dynamic processes in the early Miocene. Understanding this transformation could have important implications for the utility of the Himalayan-Tibetan system as a modern analogue for ancient orogens.
Large near-surface block rotations at normal faults of the Iceland rift: Evolution of tectonic caves and dilatancy
Authors: Kettermann Michael , Weismüller Christopher , von Hagke Christoph , Reicherter Klaus , Urai Janos L.
Published: June 2019

Surface ramps in normal fault zones of the Iceland plate boundary have been described in many studies, but their structure and evolution are not well understood. We show that surface ramps are manifestations of large tilted blocks (TBs) formed in dip relays of normal faults. Based on existing modeling studies, we propose three classes of TBs defined by kinematics and location of the hinge of the TB. TBs are considered a member of the family of fault relay structures that form near the surface, commonly, but not exclusively, in columnar basalts with orthotropic strength. We present high-resolution aerial vehicle–based observations of a representative set of normal faults in Iceland and compare these with geometric models we derived from modeling studies. We predict extensive tectonic cave (fluid conduit) systems under the TB, which interact with magma and groundwater flow. The general fault structure is dominated by large, subvertical open fractures reactivating cooling joints that are locally filled by basalt rubble. We propose the existence of a hybrid failure zone at larger depths before the effective vertical stress is sufficient to initiate shear fractures in intact basalt.
Time before return to play for the most common injuries in professional football: a 16-year follow-up of the UEFA Elite Club Injury Study
Authors: Ekstrand Jan , Krutsch Werner , Spreco Armin , van Zoest Wart , Roberts Craig , Meyer Tim , Bengtsson Håkan
Published: June 2019

Objectives

The objective was to describe the typical duration of absence following the most common injury diagnoses in professional football.

Methods

Injuries were registered by medical staff members of football clubs participating in the Union of European Football Association Elite Club Injury Study. Duration of absence due to an injury was defined by the number of days that passed between the date of the injury occurrence and the date when the medical team allowed the player to return to full participation. In total, 22 942 injuries registered during 494 team-seasons were included in the study.

Results

The 31 most common injury diagnoses constituted a total of 78 % of all reported injuries. Most of these injuries were either mild (leading to a median absence of 7 days or less, 6440 cases = 42%) or moderate (median absence: 7–28 days, 56% = 8518 cases) while only few (2% = 311 cases) were severe (median absence of >28 days). The mean duration of absence from training and competition was significantly different (p < 0.05) between index injuries and re-injuries for six diagnoses (Achilles tendon pain, calf muscle injury, groin adductor pain, hamstring muscle injuries and quadriceps muscle injury) with longer absence following re-injuries for all six diagnoses

Conclusions

The majority of all time loss due to injuries in professional football stems from injuries with an individual absence of up to 4 weeks. This article can provide guidelines for expected time away from training and competition for the most common injury types as well as for its realistic range.
Effect of a risk-stratified intervention strategy on surgical complications: experience from a multicentre prospective study in China
Authors: Yu Xiaochu , Jiang Jingmei , Shang Hong , Wu Shizheng , Sun Hong , Li Hanzhong , Xin Shijie , Zhao Shengxiu , Huang Yuguang , Wu Xinjuan , Zhang Xu , Wang Yaolei , Xue Fang , Han Wei , Wang Zixing , Hu Yaoda , Wang Lei , Zhao Yupei
Published: June 2019

Objectives

To develop a risk-stratified intervention strategy and evaluate its effect on reducing surgical complications.

Design

A multicentre prospective study with preintervention and postintervention stages: period I (January to June 2015) to develop the intervention strategy and period II (January to June 2016) to evaluate its effectiveness.

Setting

Four academic/teaching hospitals representing major Chinese administrative and economic regions.

Participants

All surgical (elective and emergent) inpatients aged ≥14 years with a minimum hospital stay of 24 hours, who underwent a surgical procedure requiring an anesthesiologist.

Interventions

Targeted complications were grouped into three categories (common, specific, serious) according to their incidence pattern, severity and preventability. The corresponding expert consensus-generated interventions, which focused on both regulating medical practices and managing inherent patient-related risks, were implemented in a patient-tailored way via an electronic checklist system.

Primary and secondary outcomes

Primary outcomes were (1) in-hospital death/confirmed death within 30 days after discharge and (2) complications during hospitalisation. Secondary outcome was length of stay (LOS).

Results

We included 51 030 patients in this analysis (eligibility rate 87.7%): 23 413 during period I, 27 617 during period II. Patients’ characteristics were comparable during the two periods. After adjustment, the mean number of overall complications per 100 patients decreased from 8.84 to 7.56 (relative change 14.5%; P<0.0001). Specifically, complication rates decreased from 3.96 to 3.65 (7.8%) for common complications (P=0.0677), from 0.50 to 0.36 (28.0%) for specific complications (P=0.0153) and from 3.64 to 2.88 (20.9%) for serious complications (P<0.0001). From period I to period II, there was a decreasing trend for mortality (from 0.64 to 0.53; P=0.1031) and median LOS (by 1 day; P=0.8293), without statistical significance.

Conclusions

Implementing a risk-stratified intervention strategy may be a target-sensitive, convenient means to improve surgical outcomes.
Cross-sectional observation study to investigate the impact of risk-based stratification on care pathways for patients with chronic kidney disease: protocol paper
Authors: Bhachu Harjeet Kaur , Cockwell Paul , Subramanian Anuradhaa , Nirantharakumar Krishnarajah , Kyte Derek , Calvert Melanie
Published: June 2019

Introduction

Chronic kidney disease (CKD) management in the UK is usually primary care based, with National Institute for Health and Care Excellence (NICE) guidelines defining criteria for referral to secondary care nephrology services. Estimated glomerular filtration rate (eGFR) is commonly used to guide timing of referrals and preparation of patients approaching renal replacement therapy. However, eGFR lacks sensitivity for progression to end-stage renal failure; as a consequence, the international guideline group, Kidney Disease: Improving Global Outcomes has recommended the use of a risk calculator. The validated Kidney Failure Risk Equation may enable increased precision for the management of patients with CKD; however, there is little evidence to date for the implication of its use in routine clinical practice. This study will aim to determine the impact of the Kidney Failure Risk Equation on the redesignation of patients with CKD in the UK for referral to secondary care, compared with NICE CKD guidance.

Method and analysis

This is a cross-sectional population-based observational study using The Health Improvement Network database to identify the impact of risk-based designation for referral into secondary care for patients with CKD in the UK. Adult patients registered in primary care and active in the database within the period 1 January 2016 to 31 March 2017 with confirmed CKD will be analysed. The proportion of patients who meet defined risk thresholds will be cross-referenced with the current NICE guideline recommendations for referral into secondary care along with an evaluation of urinary albumin–creatinine ratio monitoring.

Ethics and dissemination

Approval was granted by The Health Improvement Network Scientific Review Committee (Reference number: 18THIN061). Study outcomes will inform national and international guidelines including the next version of the NICE CKD guideline. Dissemination of findings will also be through publication in a peer-reviewed journal, presentation at conferences and inclusion in the core resources of the Think Kidneys programme.
Increasing age- and gender-specific burden and complexity of multimorbidity in Taiwan, 2003–2013: a cross-sectional study based on nationwide claims data
Authors: Hu Rey-Hsing , Hsiao Fei-Yuan , Chen Li-Ju , Huang Pei-Ting , Hsu William Wei-Yuan
Published: June 2019

Objective

Although there is accumulating evidence regarding multimorbidity in Western countries, this information is very limited in Asian countries. This study aimed to estimate population-based, age-specific and gender-specific prevalence and trends of multimorbidity in the Taiwanese population.

Design

This was a cross-sectional study based on claims data (National Health Insurance Research Database, Taiwan).

Participants

The participants included a subset of the National Health Insurance Research Database, which contains claims data for two million randomly selected beneficiaries (~10% of the total population) under Taiwan’s mandatory National Health Insurance system.

Outcome measurements

The prevalence of multimorbidity in different age groups and in both sexes in 2003 and 2013 was reported. We analysed data on the prevalence of 20 common diseases in each age group and for both sexes. To investigate the clustering effect, we used graphical displays to analyse the likelihood of co-occurrence with one, two, three, and four or more other diseases for each selected disease in 2003 and 2013.

Results

The prevalence of multimorbidity (two or more diseases) was 20.07% in 2003 and 30.44% in 2013. In 2013, the prevalence varied between 5.21% in patients aged 20–29 years and 80.96% in those aged 80–89 years. In patients aged 50–79 years, the prevalence of multimorbidity was higher in women than in men. In men, the prevalence of chronic pulmonary disease and cardiovascular-related diseases was predominant, while in women the prevalence of osteoporosis, arthritis, cancer and psychosomatic disorders was predominant. Co-occurring diseases varied across different age and gender groups.

Conclusions

The burden of multimorbidity is increasing and becoming more complex in Taiwan, and it was found to vary across different age and gender groups. Fulfilling the needs of individuals with multimorbidity requires collaborative work between healthcare providers and needs to take the age and gender disparities of multimorbidity into account.
Value-based healthcare analysis of joint replacement surgery for patients with primary hip osteoarthritis
Authors: Gabriel Lucinda , Casey Joseph , Gee Matt , Palmer Claire , Sinha Joydeep , Moxham John , Colegate-Stone Toby James
Published: June 2019

Background

A quarter of the population present at least once a year with a musculoskeletal disorder. Primary hip osteoarthritis is a high-volume condition with significant clinical need and population-level costs. There remains much variation in patient outcomes and care delivery costs for this condition.

Aims

The study aimed to gauge if pathway redesign based on the principles of value-based healthcare (VBHC) could increase value. The aim was to calculate the value of treatment for primary hip osteoarthritis through measuring outcomes that matter to patients, as well as the costs of delivering them. Additionally it aimed to compare two care pathways to identify which elements may better promote the delivery of high-value clinical care.

Methods

Two care models were evaluated: the first being a traditional model with multiple entry points and without pathway standardisation, and the second an intentionally designed standardised multidisciplinary pathway. Mandated National Health Service patient-reported outcomes were assessed but were restructured into a patient-centred format to assess the impact on pain, function and psychological outcomes. Patient-level pathway economic evaluation was performed. Using these data, outcomes were mapped against cost to calculate value.

Results

There were no significant differences in clinical outcomes between the two models. The intentionally designed model delivered better value care, having lower pathway costs. This model produced a small but inconsistent positive financial margin.

Conclusions

Intentionally designed, integrated elective services offer an opportunity to develop and evaluate VBHC models. Analysis of two care pathways from a VBHC perspective demonstrated that an intentionally designed pathway had higher value. The higher value pathway maximised the benefits of having physiotherapists and orthopaedic surgeons working side by side. Developing and measuring patient-orientated outcomes and performing accurate economic evaluation are the key to understanding and achieving better value care.
Highlights from this issue
Authors: Beattie R Mark
Published: June 2019

Click here to listen to the Podcast
Effectiveness of a collaborative, student-run campaign to increase safety belt use among adolescents
Authors: Kauffman Jeremy D , Soltani Tandis , McCullough Kelly , Vybiralova Petra , Macauley Karen , Danielson Paul D , Chandler Nicole M
Published: June 2019

Background

MVCs are the leading cause of death among adolescents. Seat belts have been shown to decrease MVC-related death. The purpose of this retrospective cohort study was to evaluate the effectiveness of a community-supported, student-run campaign to increase safety belt use among adolescents in Southwest Florida.

Methods

We reviewed results of campaigns at 14 high schools from 2012 to 2018. The primary outcome was change in rates of student-driver seat belt use over the course of each campaign. Secondary outcomes included trends in seat belt use and MVC-related fatalities over the study period. Wilcoxon signed-rank test was used to compare rates of seat belt use before and after each intervention and over the course of the study period. Multivariate logistic regression was used to estimate the independent effects of demographic covariates on outcomes.

Results

Altogether, 85 campaigns were reviewed. A total of 8500 preintervention and 8500 postintervention observations of student seat belt use were assessed. The median rate of seat belt use increased from 82% prior to the intervention to 87% following the intervention (p<0.001). We did not detect a sustained trend in seat belt use or MVC-related fatalities over the study period. On multivariate analysis, schools with a higher proportion of minority students were less likely to experience a substantial increase in seat belt use following the intervention (OR=0.17, 95% CI 0.03 to 0.84, p=0.030).

Conclusion

This collaborative campaign resulted in a modest, short-term increase in seat belt use among high school students. Future studies should evaluate which interventions are most effective and how short-term increases in seat belt use can be sustained.
Elevated serum preptin concentrations in patients with diabetic nephropathy
Authors: Wang Rui , Xue Aili , Zheng Wenjian , Wang Linchuan , Yan Fei , Hu Wenchao , Lin Jingna , He Lanjie
Published: June 2019

Preptin is a peptide synthesized and secreted accompanied with insulin from pancreatic β cells. Here, we tested the hypothesis that serum preptin concentrations are correlated with diabetic nephropathy (DN). Our study was performed in a population of 234 patients with type 2 diabetes mellitus (T2DM) and 78 healthy subjects. Patients with T2DM were divided into three groups: normoalbuminuria group (DN0, n=106), microalbuminuria group (DN1, n=90), and macroalbuminuria group (DN2, n=38) according to urine albumin to creatinine ratio (ACR). Serum preptin concentrations were significantly increased in the three T2DM subgroups than those in the controls. DN2 group showed significantly higher serum preptin concentrations compared with DN0 and DN1 groups. Moreover, DN1 group had higher serum preptin concentrations than DN0 group. Serum preptin was correlated with a higher risk of T2DM and DN after logistic regression analysis. Simply linear regression analysis demonstrated a positive correlation between serum preptin and gender, body mass index (BMI), blood urea nitrogen, creatinine, ACR, and a negative correlation between serum preptin and glomerular filtration rate, metformin, acarbose treatment. Gender, BMI, and ACR were still positively correlated with serum preptin after multiple linear regression analysis. Our findings indicate that serum preptin concentrations are associated with renal function and DN.
PGC1α repression in IPF fibroblasts drives a pathologic metabolic, secretory and fibrogenic state
Authors: Caporarello Nunzia , Meridew Jeffrey A , Jones Dakota L , Tan Qi , Haak Andrew J , Choi Kyoung M , Manlove Logan J , Prakash Y S , Tschumperlin Daniel J , Ligresti Giovanni
Published: June 2019

Idiopathic pulmonary fibrosis (IPF) is a fatal ageing-related disease linked to mitochondrial dysfunction. The present study aimed to determine whether peroxisome proliferator activated receptor gamma co-activator 1-alpha (PPARGC1A, encoding PGC1α), a master regulator of mitochondrial biogenesis, is diminished in IPF and controls pathologic fibroblast activation. Primary human IPF, control lung fibroblasts and fibroblasts sorted from bleomycin-injured mice were used to evaluate the expression and function of PGC1α. In vitro PGC1α manipulation was performed by small interfering RNA knockdown or overexpression. Fibroblast activation was assessed by quantitative PCR, Western blotting, matrix deposition, secreted cytokine array, immunofluorescence and traction force microscopy. Mitochondrial function was assessed by Seahorse analyzer and mitochondria mass and number by flow cytometry, mitochondrial DNA quantification and transmission electron microscopy (TEM). We found that PGC1α levels are stably repressed in IPF fibroblasts. After bleomycin injury in young mice, PGC1α expression drops transiently but then increases prior to fibrosis resolution. In contrast, PGC1α expression fails to recover in aged mice with persistent fibrosis. PGC1α knockdown alone in normal human lung fibroblasts reduces mitochondrial mass and function while enhancing contractile and matrix synthetic fibroblast activation, senescence-related gene expression and soluble profibrotic and prosenescence signalling. Re-expression of PGC1α in IPF fibroblasts ameliorates all of these pathological cellular functions. Pharmacological treatment of IPF fibroblasts with rosiglitazone, but not thyroid hormone, elevated PGC1α expression and attenuated fibroblast activation. The sustained repression of PGC1α and beneficial effects of its rescue in IPF fibroblasts identifies PGC1α as an important regulator of the fibroblast’s pathological state in IPF.
The Neumann problem for complex special Lagrangian equations with critical phase
Authors: Wang Jun
Published: June 2019

We study the Neumann problem for complex special Lagrangian equations with critical phase. A priori derivative estimates up to order two are established. And we obtain the existence and uniqueness theorem by the method of continuity.
Quercetin is the Active Component of Yang-Yin-Qing-Fei-Tang to Induce Apoptosis in Non-Small Cell Lung Cancer
Authors: Li Hong , Tan Ling , Zhang Jia-Wei , Chen Hong , Liang Bing , Qiu Ting , Li Qing-Song , Cai Min , Zhang Qi-Hui
Published: June 2019

Yang-Yin-Qing-Fei-Tang (YYQFT) is a well-known traditional Chinese medicine used in the treatment of chronic obstructive pulmonary emphysema, bronchitis, cytomegaloviral pneumonia, but the mechanisms of the medicine are not clear. This study aimed to identify the active components of YYQFT and elucidate the underlying mechanism on non-small cell lung cancer. First, YYQFT was extracted with different solvents, and then the most effective extract was determined by assessing their effects on non-small cell lung cancer cell growth. Second, several active compounds from YYQFT were identified, and quercetin was the one of the important active ingredients. Subsequently, the in vivo antitumor activity of quercetin was confirmed in a lung cancer xenograft model in mice. 200[Formula: see text][Formula: see text]g/mL quercetin significantly reduced tumor volume without affecting body weight of the mice. Furthermore, induction of apoptosis by quercetin was detected in tumor tissues treated with quercetin. Multiple apoptosis related genes including p53, Bax and Fas were upregulated by quercetin in tumor tissue and the ratio of Bax/Bcl-2 was increased accordingly. Our results demonstrated that quercetin, as the main effective component of the YYQFT, has potent inhibitory activity on non-small cell lung cancer by regulating the ratio of Bax/Bcl-2.
CHINA’S BELT AND ROAD INITIATIVE: A VIEW FROM A MAHATHIRIST IMAGINARY
Authors: KHOO BOO TEIK
Published: June 2019

Malaysia’s Mahathir Mohamad stands in a delicate position vis-à-vis China’s Belt and Road Initiative (BRI). The BRI’s Silk Road-like scenarios of transcontinental rail links to extend market-facilitated trade and investment have a place within a ‘Mahathirist imaginary’ that opposes inequities in a western-ruled global order and sees hope for the ‘rise of Asia’. In vision he shares the ‘Chinese Dream’ of resurrecting ancient land and maritime trade routes as an ‘imperative of globalization’ despite attempts by others to entangle the BRI in narratives of geopolitics long repugnant to his deep non-aligned convictions. His unprecedented resumption of premiership in May 2018 gave Mahathir a dream-like chance to engage with the BRI but he has been jolted by some Malaysian-China projects contracted in the name of the BRI by the Najib Razak-headed regime (2009–2018). Concerned that those projects could strain Malaysia’s debt burden and undermine its sovereignty, Mahathir must balance his support for BRI with undoing some of its local manifestations without jeopardizing long-term Malaysia-China trade, investment and diplomatic relations.
Finite-type invariants of order one of long and framed virtual knots
Authors: Petit Nicolas
Published: June 2019

We generalize three invariants, first discovered by Henrich, to the long and/or framed virtual knot case. These invariants are all finite-type invariants of order one, and include a universal invariant. The generalization will require us to extend the notion of a based matrix of a virtual string, first introduced by Turaev and later generalized by Henrich, to the long and framed cases.
Tachyon-inspired viscous inflation using Hamilton–Jacobi’s formalism during high dissipative regime
Authors: Saleem Rabia
Published: June 2019

This paper deals with warm viscous inflation inspired by tachyon field using an important inflationary method known as Hamilton–Jacobi’s Formalism. This method provides a way to solve the equations of inflationary model without using extra approximations other than slow-roll. In this scenario, a general inflationary formalism is developed for tachyon field and the work is restricted to high dissipative regime. A detailed analysis of the model is presented for three different cases of constant as well as variable bulk and dissipative coefficients. In each case, the model parameters are constrained to plot the physically acceptable range of the perturbed parameters. The parametric trajectories proved that the acquired results for all cases are compatible with Planck astrophysical data.
The system of sets of lengths and the elasticity of submonoids of a finite-rank free commutative monoid
Authors: Gotti Felix
Published: June 2019

Let [Formula: see text] be an atomic monoid. For [Formula: see text], let [Formula: see text] denote the set of all possible lengths of factorizations of [Formula: see text] into irreducibles. The system of sets of lengths of [Formula: see text] is the set [Formula: see text]. On the other hand, the elasticity of [Formula: see text], denoted by [Formula: see text], is the quotient [Formula: see text] and the elasticity of [Formula: see text] is the supremum of the set [Formula: see text]. The system of sets of lengths and the elasticity of [Formula: see text] both measure how far [Formula: see text] is from being half-factorial, i.e. [Formula: see text] for each [Formula: see text].

Let [Formula: see text] denote the collection comprising all submonoids of finite-rank free commutative monoids, and let [Formula: see text]. In this paper, we study the system of sets of lengths and the elasticity of monoids in [Formula: see text]. First, we construct for each [Formula: see text] a monoid in [Formula: see text] having extremal system of sets of lengths. It has been proved before that the system of sets of lengths does not characterize (up to isomorphism) monoids in [Formula: see text]. Here we use our construction to extend this result to [Formula: see text] for any [Formula: see text]. On the other hand, it has been recently conjectured that the elasticity of any monoid in [Formula: see text] is either rational or infinite. We conclude this paper by proving that this is indeed the case for monoids in [Formula: see text] and for any monoid in [Formula: see text] whose corresponding convex cone is polyhedral.
A Stochastic Galerkin Cell-based Smoothed Finite Element Method (SGCS–FEM)
Authors: Mathew Tittu Varghese , Beex Lars , Bordas Stéphane PA , Natarajan Sundararajan
Published: June 2019

In this paper, the cell-based smoothed finite element method is extended to solve stochastic partial differential equations with uncertain input parameters. The spatial field of Young’s Modulus and the corresponding stochastic results are represented by Karhunen-Loéve expansion and polynomial chaos expansion, respectively. Young’s Modulus of structure is considered to be random for stochastic static as well as free vibration problems. Mathematical expressions and the solution procedure are articulated in detail to evaluate the statistical characteristics of responses in terms of the static displacements and the free vibration frequencies. The feasibility and the effectiveness of the proposed SGCS–FEM method in terms of accuracy and lower demand on the mesh size in the solution domain over that of conventional FEM for stochastic problems are demonstrated by carefully chosen numerical examples. From the numerical study, it is inferred that the proposed framework yields accurate results.
Preparation of star-shaped functionalized polylactides by metal porphyrin complexes as both catalysts and cocatalysts
Authors: Li Dongni , Gao Bo , Duan Qian
Published: June 2019

Several aluminum porphyrin complexes as catalysts and a copper porphyrin complex as a cocatalyst were prepared. These complexes were characterized by 1H NMR and elemental analysis. These complexes are used for L-lactide polymerization. The kinetic data of the polymerization using complex 2 as catalyst revealed that the polymeric rates were first-ordered in both the monomer and catalyst. There is a linear relationship between lactide conversion and the number-averaged molecular weight of PLA.