bluuebunny/crossref_metadata_2025 huggingface dataset:
LKB1 coordinates neurite remodeling to drive synapse layer emergence in the outer retina
Authors: Burger Courtney A , Alevy Jonathan , Casasent Anna K , Jiang Danye , Albrecht Nicholas E , Liang Justine H , Hirano Arlene A , Brecha Nicholas C , Samuel Melanie A
Published: May 2020

Structural changes in pre and postsynaptic neurons that accompany synapse formation often temporally and spatially overlap. Thus, it has been difficult to resolve which processes drive patterned connectivity. To overcome this, we use the laminated outer murine retina. We identify the serine/threonine kinase LKB1 as a key driver of synapse layer emergence. The absence of LKB1 in the retina caused a marked mislocalization and delay in synapse layer formation. In parallel, LKB1 modulated postsynaptic horizontal cell refinement and presynaptic photoreceptor axon growth. Mislocalized horizontal cell processes contacted aberrant cone axons in LKB1 mutants. These defects coincided with altered synapse protein organization, and horizontal cell neurites were misdirected to ectopic synapse protein regions. Together, these data suggest that LKB1 instructs the timing and location of connectivity in the outer retina via coordinate regulation of pre and postsynaptic neuron structure and the localization of synapse-associated proteins.
Driving polar growth
Authors: Dhar Neeraj
Published: May 2020

Profiling the phenotype of 200,000 mutants revealed a new cofactor that may help a group of rod-shaped bacteria elongate and grow.
Health care rationing in Italy: right to health vs. budget constraints in a regional-based health system
Authors: Santuari Alceste
Published: May 2020

After the enactment of the 2001 Constitutional Reform Act, the Italian health system consists of as many as 21 regional health systems. The central government retains the public task of ensuring that all citizens, regardless of their territorial residence, may access the same universal
and equitable health services and provisions.
 After the economic crisis of 2007/2008, as has been the case in many other EU MSs, the Italian central government has decreased public expenditure on health care. Not only has such an approach undermined citizens' fundemental right to
health. It has also triggered a fierce confrontation between regional governments and the State, which has also been the object of some rulings of the Italian Supreme Court.
 Against this background, the paper aims to analyse the impacts that health care rationing has on the organisation
of health and care services and on the evolution of social enterprises as health providers.
Rationing in the English NHS and the Tension between Patient Choice and Solidarity
Authors: Sheppard Maria K.
Published: May 2020

Solidarity is a principle that underlies the English National Health Service (NHS). While intended to be comprehensive, since its inception financial constraints meant that limits have been placed on the availability of NHS health care. Health care has been rationed in a number of ways
but English law demands that any such rationing policies by public bodies must allow for exceptions in special cases. When a patient makes an individual funding request (IFR) for such a treatment it is a question for the health authority to decide on the merits of the IFR whereas in any subsequent
judicial review proceedings the court considers that decision in terms of its legitimacy, procedural propriety and reasonableness. To avoid judicial review of decisions health authorities are often inclined to accede to patients' requests because litigation, apart from being costly and time-consuming
for the authority, also sets new precedents. This has led to suggestions that solidarity is being eroded in the NHS since resources that are spent on such requests by patients mean disinvestment from other areas of the NHS. This paper argues that enabling individual choice may in effect support
a collective commitment to a solidaristic health care system. Rather than encroaching on the principle of solidarity (intended) litigation by patients destabilises the health care system and leads to much needed change and reform. Not only do the potential ramifications of (intended) litigation
go beyond the immediate consequences for the parties to the action, but the need to account for rationing decisions by the health authority in public makes the system accessible to broader interests. Patient treatment choice can thus be seen as an affirmation of a commitment to solidarity
that is also supported by the increased emphasis on patients taking responsibility for their own health with the aim of reducing NHS costs.
Integrated analysis of lymphocyte infiltration-associated lncRNA for ovarian cancer via TCGA, GTEx and GEO datasets
Authors: Wu Meijing , Shang Xiaobin , Sun Yue , Wu Jing , Liu Guoyan
Published: May 2020

Background

Abnormal expression of long non-coding RNAs (lncRNA) play a significant role in the incidence and progression of high-grade serous ovarian cancer (HGSOC), which is a leading cause of mortality among gynecologic malignant tumor patients. In this study, our aim is to identify lncRNA-associated competing endogenous RNA (ceRNA ) axes that could define more reliable prognostic parameters of HGSOC, and to investigate the lncRNAs’ potential mechanism of in lymphocyte infiltration.

Methods

The RNA-seq and miRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database; while for obtaining the differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs), we used edgeR, limma and DESeq2. After validating the RNA, miRNA and gene expressions, using integrated three RNA expression profiles (GSE18520, GSE27651, GSE54388) and miRNA profile (GSE47841) from the Gene Expression Omnibus (GEO) database, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses through ClusterProfiler. The prognostic value of these genes was determined with Kaplan–Meier survival analysis and Cox regression analysis. The ceRNA network was constructed using Cytoscape. The correlation between lncRNAs in ceRNA network and immune infiltrating cells was analyzed by using Tumor IMmune Estimation Resource (TIMER), and gene markers of tumor-infiltrating immune cells were identified using Spearman’s correlation after removing the influence of tumor purity.

Results

A total of 33 DELs (25 upregulated and eight downregulated), 134 DEMs (76 upregulated and 58 downregulated), and 1,612 DEGs (949 upregulated and 663 downregulated) were detected that could be positively correlated with overall survival (OS) of HGSOC. With the 1,612 analyzed genes, we constructed a ceRNA network, which indicated a pre-dominant involvement of the immune-related pathways. Furthermore, our data revealed that LINC00665 influenced the infiltration level of macrophages and dendritic cells (DCs). On the other hand, FTX and LINC00665, which may play their possible roles through the ceRNA axis, demonstrated a potential to inhibit Tregs and prevent T-cell exhaustion.

Conclusion

We defined several prognostic biomarkers for the incidence and progression of HGSOC and constructed a network for ceRNA axes; among which three were indicated to have a positive correlation with lymphocyte infiltration, namely: FTX-hsa-miR-150-5p-STK11, LINC00665-hsa-miR449b-5p-VAV3 and LINC00665-hsa-miR449b-5p-RRAGD.
Association of heart rate trajectories with the risk of adverse outcomes in a community-based cohort in Taiwan
Authors: Wei Cheng-Chun , Chen Pei-Chun , Hsu Hsiu-Ching , Su Ta-Chen , Lin Hung-Ju , Chen Ming-Fong , Lee Yuan-Teh , Chien Kuo-Liong
Published: May 2020

Heart rate trajectory patterns integrate information regarding multiple heart rate measurements and their changes with time. Different heart rate patterns may exist in one population, and these are associated with different outcomes. Our study investigated the association of adverse outcomes with heart rate trajectory patterns. This was a prospective cohort study based on the Chin-Shan Community Cardiovascular Cohort in Taiwan. A total of 3,015 Chinese community residents aged > 35 years were enrolled in a prospective investigation of cardiovascular risk factors and outcomes from 1990 to 2013.The primary outcome was all-cause mortality, and the secondary outcome was a composite of coronary artery disease and cerebrovascular accidents. The following trajectory patterns were identified: stable, 61%; decreased, 5%; mildly increased, 32%; and markedly increased, 2%. During follow-up (median, 13.9 years), 557 participants died and 217 experienced secondary outcomes. The adjusted hazard ratios of primary and secondary outcomes for participants with a markedly increased trajectory pattern were 1.80 (95% CI [1.18–2.76]) and 1.45 (95% CI [0.67–3.12]), respectively, compared to those for participants with a stable trajectory pattern. A markedly increased heart rate trajectory pattern may be associated with all-cause mortality risks. Heart rate trajectory patterns demonstrated the utility of repeated heart rate measurements for risk assessment.
Public perspectives and media reporting of wolf reintroduction in Colorado
Authors: Niemiec Rebecca , Berl Richard E.W. , Gonzalez Mireille , Teel Tara , Camara Cassiopeia , Collins Matthew , Salerno Jonathan , Crooks Kevin , Schultz Courtney , Breck Stewart , Hoag Dana
Published: May 2020

In the state of Colorado, a citizen ballot initiative to reintroduce gray wolves (Canis Lupus) is eliciting polarization and conflict among multiple stakeholder and interest groups. Given this complex social landscape, we examined the social context surrounding wolf reintroduction in Colorado as of 2019. We used an online survey of 734 Coloradans representative in terms of age and gender, and we sampled from different regions across the state, to examine public beliefs and attitudes related to wolf reintroduction and various wolf management options. We also conducted a content analysis of media coverage on potential wolf reintroduction in 10 major daily Colorado newspapers from January 2019, when the signature-gathering effort for the wolf reintroduction initiative began, through the end of January 2020, when the initiative was officially added to the ballot. Our findings suggest a high degree of social tolerance or desire for wolf reintroduction in Colorado across geographies, stakeholder groups, and demographics. However, we also find that a portion of the public believes that wolves would negatively impact their livelihoods, primarily because of concerns over the safety of people and pets, loss of hunting opportunities, and potential wolf predation on livestock. These concerns—particularly those related to livestock losses—are strongly reflected in the media. We find that media coverage has focused only on a few of the many perceived positive and negative impacts of wolf reintroduction identified among the public. Our findings highlight the need to account for this diversity of perspectives in future decisions and to conduct public outreach regarding likely impacts of wolf reintroduction.
Evaluation of a novel syndromic surveillance system for the detection of the 2007 melamine-related nephrotoxicosis foodborne outbreak in dogs and cats in the United States
Authors: Weng Hsin-Yi , Gaona Mark A.L. , Kass Philip H.
Published: May 2020

The 2007 nephrotoxicosis outbreak associated with melamine and cyanuric acid adulteration of pet foods in the United States sparked an urgent need for a nationwide companion animal surveillance program. In 2016, we introduced a syndromic surveillance system based on a novel epidemiological algorithm, the proportionate diagnostic outcome ratio (PDOR). The PDOR procedure was validated using simulated outbreaks of foodborne illness (i.e., aflatoxicosis and gastrointestinal illness) in dogs and cats. In this study, we further evaluated the PDOR procedure using the 2007 melamine-related outbreak of nephrotoxicosis. The performance of the PDOR procedure was assessed by the time to alert and positive predictive value (PPV). Electronic medical records of dogs and cats seen at networked primary care veterinary hospitals across the United States were retrieved from a centralized database. The data of four relevant syndromic components: elevated serum creatinine concentration, vomiting, anorexia, and lethargy from July 28, 2006 to May 31, 2007 were prospectively analyzed using the PDOR algorithm. The results showed that the alerts generated from the analysis of elevated serum creatinine concentration could have led to an early detection of this nephrotoxicosis foodborne outbreak and were well matched to the reported timeline of the outbreak. Additionally, we also observed variations in the performance of the PDOR procedure across age of animals and syndromic components, with the PPVs ranged from 0.61 to 1.0. Combined with the findings from previous evaluations using simulated outbreak scenarios, this study provided additional evidence that the PDOR procedure can be applied in syndromic surveillance to effectively and accurately detect various types of foodborne illness outbreaks in companion animals. However, the interpretations of and responses to alerts require an understanding of clinical veterinary medicine and relevant syndromic knowledge, and should not be based solely on quantitative measures.
A Study on the Characteristics of Chemical Accidents and Reduction of Accidents in Jeollabuk-do
Authors: Jeong Jae-Uk , Park Chong-Eun
Published: May 2020

This study aimed to identify the characteristics of 40 chemical accidents that occurred in Jeollabuk-do from 2004 to 2019. During this time, there were 2.5 accidents per year on average in the province; their types were classified as spill/leak, fire, explosion, adverse reaction, and complex. There were 34 leaks and six explosions, and they are categorized as follows: 12 by worker error, 16 from facility defects, and 12 by transport vehicle accidents. The substances involved in these accidents were ammonia (15%), sulfuric acid (12.5%), and silicon tetrachloride (7.5%). Notably, the rate of chemical accidents (75%) is the highest during spring and summer. In order to reduce chemical accidents, first, there should be compliance with the relevant laws. Second, the quality of safety education and training of workers should be improved. Finally, valuable government support is also necessary to improve facilities.
An Analysis on the Effects of Educational Training of New Fire Officers on Job Implementation
Authors: Chae Jin
Published: May 2020

Existing verification research for how effectively the educational training of new fire officers has been applied to actual fieldwork is extremely insignificant. This is because only a few studies have empirically verified job implementation according to job satisfaction, which is believed to have a great influence on various aspects such as learner traits, educational programs, and learning outcomes. Moreover, it is necessary to conduct an empirical investigation regarding the effects of learner traits, educational programs, and learning outcomes on disaster scenes and the job implementation of fire administration on new fire officers. This study aims to provide an empirical analysis of the effects of educational training of new fire officers on job implementation. It has been identified that learner traits and learning outcomes have an effect on job satisfaction. Accordingly, job satisfaction, educational programs, learning outcomes, and learner traits have a significant effect (P < 0.05) on job implementation.
Clozapine and hematologic adverse reactions: Impact of the Risk Evaluation and Mitigation Strategy program
Authors: Borrelli Eric P. , Lee Erica Y. , Caffrey Aisling R.
Published: May 2020

Introduction

In October 2015, the Food and Drug Administration (FDA) instituted an update to the mandatory Risk Evaluation and Mitigation Strategy (REMS) program for clozapine to improve safety monitoring of hematologic events. However, the impact of the clozapine REMS program on reporting of hematologic adverse events has not been quantified.

Methods

We assessed adverse event reports for agranulocytosis, granulocytopenia, leukopenia, and neutropenia from the FDA Adverse Event Reporting System (FAERS) for a 1-year time period before (October 2014 to September 2015, pre-REMS) and after (October 2015 to September 2016, post-REMS) the implementation of the clozapine REMS program. The AERSMine platform was used to capture historical effect estimates (October 2004 to September 2014). Reporting odds ratios (ROR), proportional reporting ratios (PRR), and corresponding Taylor series 95% confidence intervals (CIs) were calculated for hematologic events with clozapine compared with all other medications using OpenEpi.

Results

Reporting rates for agranulocytosis, granulocytopenia, leukopenia, and neutropenia with clozapine all increased from the pre-REMS to post-REMS time frames, ranging from a 2-fold increase with leukopenia to a 40-fold increase with neutropenia; the composite measure of all hematologic reports had a 12-fold increase. During the post-REMS time frame, the ROR increased by 1691% (111.4, 95% CI 100.6-123.4) compared with the pre-REMS time frame (7.1, 95% CI 5.2-9.6), and the PRR increased by 1280% (83.1, 95% CI 76.8-90.0 vs 6.9, 95% CI 5.1-9.4) for the composite outcome.

Discussion

We observed significant increases in reports of hematologic adverse events with clozapine after the introduction of the clozapine REMS program. Future research should explore the impact of the less stringent exclusionary and discontinuation criteria on utilization (eg, expanded access) and clinical outcomes (eg, treatment effectiveness and adverse events).
Desvenlafaxine-associated hyperglycemia: A case report and literature review
Authors: Mekonnen Andrea D. , Mills Aubrey A. , Wilhite Andrea L. , Hoffman Theresa K.
Published: May 2020

Desvenlafaxine is a potent selective serotonin and norepinephrine reuptake inhibitor used to treat depression and anxiety. Several antidepressants have been associated with drug-induced hyperglycemia, but currently there are no reports for desvenlafaxine. A case of suspected desvenlafaxine-induced hyperglycemia is presented involving a 59-year-old female with type 2 diabetes whose average blood glucose increased by 30 mg/dL for fasting blood glucose and 75 mg/dL for postprandial blood glucose 1 month after switching from venlafaxine to desvenlafaxine. Prior to starting desvenlafaxine, she was stable on metformin 1000 mg twice daily, insulin glargine 8 units daily, and dulaglutide 1.5 mg once weekly. Over the course of 3 months after desvenlafaxine initiation, insulin glargine was increased and insulin lispro was initiated as the patient refused alternative antidepressant therapy due to favorable improvements in anxiety and depression. No other cause for elevated blood glucose could be elucidated. The Naranjo scale resulted in a score of 3, indicating a possible cause for the adverse drug reaction. Antidepressants have been associated with glucose dysregulation. However, literature also demonstrates improved glycemic control in treated versus untreated depression. If altered glucose levels are noted, all potential causative factors should be evaluated and risks and benefits weighed to guide therapy.
Stiff-person syndrome in a patient with comorbid bipolar and panic disorders: A case report and literature review
Authors: Patel Karishma , Stummer Lauren , Patel Krina
Published: May 2020

Stiff-person syndrome (SPS) is a neurologic disorder characterized by muscle stiffness, rigidity, and muscle spasms, and it can increase a patient's risk for falls. It is recognized as a rare disease with limited clinical guidelines to manage the condition and its symptoms. Currently, there is even less clinical guidance for the management of common comorbid conditions in these patients. This patient case report aims to evaluate the efficacy of various medications for symptom management in a patient with SPS and comorbid psychiatric disorders, specifically bipolar I and panic disorder. Throughout the patient's course of treatment, various medications were trialed, including fluoxetine, hydroxyzine, valproic acid, propranolol, and clonazepam. Ultimately, fluoxetine, hydroxyzine, and propranolol were discontinued due to adverse drug reactions and incomplete symptom resolution. The patient's bipolar I disorder was adequately managed with valproic acid. Once the clonazepam was changed from as-needed to scheduled dosing, the patient's panic disorder and anxiety-triggered spasms were well controlled. The efficacy of benzodiazepines, specifically high doses of diazepam, in alleviating muscle spasms and anxiety in SPS has been demonstrated in the literature. Case reports including patients with SPS that are prescribed selective serotonin reuptake inhibitors provide controversial evidence as some studies report exacerbation of SPS symptoms with prolonged use. As this case report and literature review suggest, patients with SPS and comorbid panic disorder and anxiety-triggered spasms may benefit from the use of benzodiazepines. The use of other medication classes for the treatment of other comorbid psychiatric disorders in a patient with SPS is lacking evidence.
Knowledge‐based structural models of SARS‐CoV‐2 proteins and their complexes with potential drugs
Authors: Hijikata Atsushi , Shionyu‐Mitsuyama Clara , Nakae Setsu , Shionyu Masafumi , Ota Motonori , Kanaya Shigehiko , Shirai Tsuyoshi
Published: May 2020

The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID‐19) caused by the novel coronavirus SARS‐CoV‐2 a pandemic. There is, however, no confirmed anti‐COVID‐19 therapeutic currently. In order to assist structure‐based discovery efforts for repurposing drugs against this disease, we constructed knowledge‐based models of SARS‐CoV‐2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID‐19.
High Flexible and Broad Antibacterial Nanodressing Induces Complete Skin Repair with Angiogenic and Follicle Regeneration
Authors: Hu Weikang , Wang Zijian , Zha Yao , Gu Xiang , You Wenjie , Xiao Yu , Wang Xinghuan , Zhang Shengmin , Wang Jianglin
Published: May 2020

Complete skin reconstruction is a hierarchically physiological assembly involving epidermis, dermis, vasculature, innervation, hair follicles, and sweat glands. Despite various wound dressings having been developed for skin regeneration, few works refer to the complete skin regeneration, particularly lacking for vasculatures and hair follicles. Herein, an instructive wound dressing that integrates the antibacterial property of quaternized chitin and the mechanical strength and biological multifunction of silk fibroin through layer‐by‐layer electrostatic self‐assembly is designed and reported. The resultant dressings exhibit a nanofibrous structure ranging from 471.5 ± 212.1 to 756.9 ± 241.8 nm, suitable flexibility with tensile strength up to 4.47 ± 0.29 MPa, and broad‐spectrum antibacterial activity against Escherichia coli and Staphylococcus aureus. More interestingly, the current dressing system remarkably accelerates in vivo vascular reconstruction within 15 days, and the number of regenerated hair follicles reaches up to 22 ± 4 mm−2, which is comparable to the normal tissue (27 ± 2 mm−2). Those crucial functions might originate from the combination between quaternized chitin and silk fibroin and the hierarchical structure of electrospun nanofiber. This work establishes an easy but effective pathway to design a multifunctional wound dressing for the complete skin regeneration.
Bioengineered Hybrid Collagen Scaffold Tethered with Silver‐Catechin Nanocomposite Modulates Angiogenesis and TGF‐β Toward Scarless Healing in Chronic Deep Second Degree Infected Burns
Authors: Kalirajan Cheirmadurai , Palanisamy Thanikaivelan
Published: May 2020

Management of burn wounds with diabetes and microbial infection is challenging in tissue engineering. The delayed wound healing further leads to scar formation in severe burn injury. Herein, a silver‐catechin nanocomposite tethered collagen scaffold with angiogenic and antibacterial properties is developed to enable scarless healing in chronic wounds infected with Pseudomonas aeruginosa under diabetic conditions. Histological observations of the granulation tissues collected from an experimental rat model show characteristic structural organizations similar to normal skin, whereas the open wound and pristine collagen scaffold treated animals display elevated dermis with thick epidermal layer and lack of appendages. Epidermal thickness of the hybrid scaffold treated diabetic animals is lowered to 33 ± 2 µm compared to 90 ± 2 µm for pristine collagen scaffold treated groups. Further, the scar elevation index of 1.3 ± 0.1 estimated for the bioengineered scaffold treated diabetic animals is closer to the normal skin. Immunohistochemical analyses provide compelling evidence for the enhanced angiogenesis as well as downregulated transforming growth factor‐ β1 (TGF‐β1) and upregulated TGF‐β3 expressions in the hybrid scaffold treated animal groups. The insights from this study endorse the bioengineered collagen scaffolds for applications in tissue regeneration without scar in chronic burn wounds.
Bifunctional Nanomaterials for Enhanced Cell Proliferation and for the Reduction of Bacterial Bioluminescence/Fitness
Authors: Motealleh Andisheh , Czieborowski Michael , Philipp Bodo , Nowak Sascha , Kehr Nermin S.
Published: May 2020

This study describes the synthesis of bifunctional nanomaterials that can both inhibit bacterial bioluminescence, an indicator for the bacterial fitness, and, simultaneously, improve the proliferation of eukaryotic cells, a property that is desired for biomedical devices such as implants. To prepare this functional nanomaterial, the pores of the periodic mesoporous organosilica (PMO) nanocontainers are first functionalized with dexamethasone (Dex), which has anti‐inflammatory and cell proliferation properties. Then, the external surface of the PMO is functionalized with the antibacterial and cell adhesive bipolymer poly‐d‐lysine (PDL). The results show that cofunctionalization of the PMO surfaces with both Dex and PDL have beneficial additive and/or synergistic effects on cell proliferation and bacterial bioluminescence inhibition.
The Application of Electron Backscatter Diffraction on Halide Perovskite Materials
Authors: Sun Hongyu , Adhyaksa Gede W.P. , Garnett Erik C.
Published: May 2020

Recently, the application of electron backscatter diffraction (EBSD) in halide perovskites has enabled the correlation of the micro‐structural arrangement of polycrystalline grains with other properties (optical, electrical, mechanical, and chemical) in a “pixel‐by‐pixel” approach. Most studies so far have used an ultra‐sensitive electron beam detector that has sensitivity thousands of times higher than a traditional scintillator screen and charge coupled device camera, enabling much lower beam currents. An alternative approach has been the use of low vacuum measurement conditions to avoid charge buildup that leads to damage. This review focuses on introducing the classical EBSD technique to the halide perovskite community, where it has been highly underutilized due to beaminduced damage in these relatively unstable materials. Recent research is used to dispel some common misconceptions about grain boundaries in halide perovskites and highlight what has been learned by comparing and correlating EBSD with other techniques. Additionally, the remaining limitations, development challenges, and future of the EBSD technique for halide perovskites are discussed. Successful utilization of the EBSD technique as a common characterization tool in the halide perovskite community will enable scientists and engineers to develop maps of cross correlated properties, helping to unlock the full potential of this complex material system.
Biomass allocation for vegetative and reproductive growth of Fritillaria przewalskii Maxim
Authors: Ma Ruili , Xu Shengrong , Chen Yuan , Guo Fengxia , Wu Rui
Published: May 2020

Fritillaria przewalskii Maxim., a member of the Lilly family native in China, is used in Chinese herbal medicine. The plants have a reproductive cycle of 6 years. In order to better understand the growth characteristics of this species, the biomass allocation for plant organs at vegetative growth stages (V) and reproductive growth stages (R) were investigated. A reduced major axis (RMA) was used to analyze biomass allometric relationship between whole plants and bulbs/leaves, between bulbs and leaves/roots, between aboveground and belowground parts. Similar biomass allocation patterns over individual organs for plants were found during V and R. At both stages, most biomass accumulated in bulbs and least in roots. All organs displayed a similar growth partitioning for both stages of growth. The results showed that the differences of biomass allocation were affected by the plants size and the growth stages during growth and development of Fritillaria przewalskii Maxim.
Associations between exposure to ethylene oxide, job termination, and cause‐specific mortality risk
Authors: Park Robert M.
Published: May 2020

Background

Previous analyses of mortality were conducted in a large cohort of ethylene oxide (EtO) exposed workers employed at 13 sterilization facilities throughout the U.S. and followed from the start of operation through 1998. Statistically significant elevated mortality was reported from hematopoietic cancer in men and breast cancer in women compared to the general population. Possible healthy worker survivor bias was not addressed.

Methods

To examine survivor bias in this cohort, employment termination was analyzed with statistical models stratified on sex and race that included age, employment duration, and cumulative EtO exposure. To reduce survivor bias employment duration was included in Poisson regression model specifications for estimating standardized mortality ratios for several cancer outcomes.

Results

Strong statistically significant effects of unlagged cumulative EtO exposure were observed on rate of employment termination, indicating potential healthy worker survivor effect bias. Adjustment for employment duration in analyses of mortality resulted in statistically significant and stronger associations between cumulative EtO exposure and lung cancer, female breast cancer and hematopoietic cancer. There was a striking reduction in nonmalignant respiratory disease mortality risk with increasing employment duration with a further (nonsignificant) reduction with cumulative EtO, suggesting that EtO itself is driving termination of workers with respiratory morbidity even though the average EtO exposures in this population were generally far below odor and acute irritancy thresholds.

Conclusions

Important survivor bias was present in this EtO cohort and may be present in many occupational settings involving irritant exposures.
Synthesis and Characterization of Anionic Poly(cyclopentadienylene vinylene) and Its Use in Conductive Hydrogels
Authors: Lee Daniel C. , Sellers Drew L. , Liu Fan , Boydston Andrew J. , Pun Suzie H.
Published: May 2020

The use of π‐conjugated polymers (CPs) in conductive hydrogels remains challenging due to the water‐insoluble nature of most CPs. Conjugated polyelectrolytes (CPEs) are promising alternatives because they have tunable electronic properties and high water‐solubility, but they are often difficult to synthesize and thus have not been widely adopted. Herein, we report the synthesis of an anionic poly(cyclopentadienylene vinylene) (aPCPV) from an insulating precursor under mild conditions and in high yield. Functionalized aPCPV is a highly water‐soluble CPE that exhibits low cytotoxicity, and we found that doping hydrogels with aPCPV imparts conductivity. We also anticipate that this synthetic strategy, due to its ease and high efficiency, will be widely used to create families of not‐yet‐explored π‐conjugated vinylene polymers.
Carbon–Carbon Bond Forming Reactions Promoted by Aluminyl and Alumoxane Anions: Introducing the Ethenetetraolate Ligand
Authors: Anker Mathew D. , McMullin Claire L. , Rajabi Nasir A. , Coles Martyn P.
Published: May 2020

[K{Al(NONDipp)}]2(NONDipp=[O(SiMe2NDipp)2]2−, Dipp=2,6‐iPr2C6H3) reacts with CS2to afford the trithiocarbonate species [K(OEt2)][Al(NONDipp)(CS3)]1or the ethenetetrathiolate complex, [K{Al(NONDipp)(S2C)}]2[3]2. The dimeric alumoxane [K{Al(NONDipp)(O)}]2reacts with carbon monoxide to afford the oxygen analogue of3, [K{Al(NONDipp)(O2C)}]2[4]2containing the hitherto unknown ethenetetraolate ligand, [C2O4]4−.
Ternary Sn‐Ti‐O Electrocatalyst Boosts the Stability and Energy Efficiency of CO2 Reduction
Authors: Wen Guobin , Ren Bohua , Park Moon G. , Yang Jie , Dou Haozhen , Zhang Zhen , Deng Ya‐Ping , Bai Zhengyu , Yang Lin , Gostick Jeff , Botton Gianluigi A. , Hu Yongfeng , Chen Zhongwei
Published: May 2020

Simultaneously improving energy efficiency (EE) and material stability in electrochemical CO2 conversion remains an unsolved challenge. Among a series of ternary Sn‐Ti‐O electrocatalysts, 3D ordered mesoporous (3DOM) Sn0.3Ti0.7O2 achieves a trade‐off between active‐site exposure and structural stability, demonstrating up to 71.5 % half‐cell EE over 200 hours, and a 94.5 % Faradaic efficiency for CO at an overpotential as low as 430 mV. DFT and X‐ray absorption fine structure analyses reveal an electron density reconfiguration in the Sn‐Ti‐O system. A downshift of the orbital band center of Sn and a charge depletion of Ti collectively facilitate the dissociative adsorption of the desired intermediate COOH* for CO formation. It is also beneficial in maintaining a local alkaline environment to suppress H2 and formate formation, and in stabilizing oxygen atoms to prolong durability. These findings provide a new strategy in materials design for efficient CO2 conversion and beyond.
A Predictive Model for Assessment of the Risk of Mold Growth in Rapeseeds Stored in a bulk as a Decision Support Tool for Postharvest Management Systems
Authors: Wawrzyniak Jolanta
Published: May 2020

Reliable prediction of the risk of mold development in a stored bulk of rapeseeds may help to maintain seed quality and ensure the highest quality and safety of cooking oil. Mathematical models based on predictive microbiology that are able to assess the risk of fungal growth and the mycotoxins formation in a stored seed ecosystems are promising prognostic tools, which may improve postharvest management systems. The aim of the study was to develop a predictive model of fungal growth in bulks of rapeseeds stored under conditions, in which seeds are at risk of quality deterioration. It was formulated on the basis of data reflecting actual seed ecosystems with a hazardous initial level of mold spores (characteristic of seeds that vegetate and are harvested under adverse weather conditions) stored at a wide range of temperature (12–30 °C) and humidity (seed water activity, aw = 0.80–0.90). The predictive model was based on the modified Gompertz equation, whose coefficients are related with biological parameters of mold growth (i.e., lag phase duration, maximum growth rate and fungal population level at the stationary phase). The biological parameters of the model were described using the second‐degree polynomial functions of temperature and water activity. The criteria used to assess the model efficiency pointed to its good predictive quality (R2 = 0.90; RMSE =0.547). Moreover, the model was characterized by high accuracy (bias factor B
f = 1.045 and accuracy factor A
f = 1.050). The formulated model of fungal growth can be used as a decision support tool to improve systems managing postharvest seed preservation processes.
A novel method for quantifying femoral neck anteversion: A case study in extinct and extant sloths
Authors: Harper Christine M. , Sylvester Adam D. , McAfee Robert K. , Cooke Siobhán B.
Published: May 2020

Extinct sloths represent a wide range of morphological, locomotor, and body size variation. Researchers have examined femoral neck angle in two dimensions to hypothesize locomotor behaviors in this group; however, this measure does not account for femoral neck anteversion. Here, we present a new method for quantifying femoral neck anteversion angle, in addition to femoral neck angle, to capture the 3D position of the femoral head/neck. Femora of extant (n= 21;BradypusandCholoepus) and extinct (n= 49;Acratocnus,Megalocnus,Neocnus, andParocnus) sloths were surface scanned and their surface models used to calculate three angles of femoral neck anteversion and femoral neck angle. Femoral neck anteversion was calculated as the angle between the femoral neck axis and the geometric axis of the femoral condyles (GA), the 35% cross section axis, and a trochanter axis. Femoral neck angle was calculated as the angle between the femoral neck and shaft axes. Genera were compared using ANOVAs with post hoc multiple comparisons for each angle. Femoral neck angle and femoral neck anteversion relative to the cross section were also analyzed. Significant differences among genera exist for all angles, (p < .001) but not all angles separate all genera. Femoral neck and anteversion angles typically yield different results, demonstrating the utility of analyzing both angles. The GA and cross section angles are highly correlated in sloths, with the exception of comparisons amongMegalocnus,Parocnus, andNeocnus, suggesting morphological variation in the distal femur. While this method was applied to sloths, it has broad applicability to mammalian groups.
Outcomes for high-risk hepatoblastoma in a resource-challenged setting
Authors: Rammohan A , Rela M , Kumar G V , Scott J X , Shanmugam N , Reddy M S , Ramachandran P
Published: May 2020

Background

Outcomes of high-risk hepatoblastoma have been dismal, especially in resource-challenged countries where access to chemotherapy and paediatric liver transplantation is limited for the underprivileged. This study aimed to assess the results of treatment of high-risk hepatoblastoma in a tertiary centre, including patients who had non-transplant surgical procedures in the form of extended resection.

Methods

A review of patients with high-risk hepatoblastoma treated between January 2012 and May 2018 was carried out. Perioperative data and long-term outcomes were analysed.

Results

Of 52 children with hepatoblastoma, 22 were considered to have high-risk hepatoblastoma (8 girls and 14 boys). The mean(s.d.) age at diagnosis was 35(20) months. Of these 22 children, five died without surgery. Of the remaining 17 who underwent surgery, six had a resection (4 right and 2 left trisectionectomies) and 11 underwent living-donor liver transplantation. Median follow-up was 48 (range 12–90) months. Thirteen of the 17 children were alive at last follow-up and four developed disseminated disease (3 had undergone liver transplantation and 1 liver resection). The overall survival rate at 1, 3 and 5 years was 77, 64 and 62 per cent for the whole cohort with high-risk hepatoblastoma. In children who had surgery, 1-, 3- and 5-year survival rates were 91, 82 and 73 per cent for transplantation and 100, 83 and 83 per cent for resection. There was no difference in survival between the two surgical groups.

Conclusion

Excellent results in the treatment of high-risk hepatoblastoma are possible, even in resource-challenged countries.
Copper‐Mediated Conversion of Complex Ethers to Esters: Enabling Biopolymer Depolymerisation under Mild Conditions
Authors: Xiao Ganyuan , Montgomery James R. D. , Lancefield Christopher S. , Panovic Isabella , Westwood Nicholas J.
Published: May 2020

Selective processing of the β‐O‐4 unit in lignin is essential for the efficient depolymerisation of this biopolymer and therefore its successful integration into a biorefinery set‐up. An approach is described in which this unit is modified to incorporate a carboxylic ester with the goal of enabling the use of mild depolymerisation conditions. Inspired by preliminary results using a Cu/TEMPO/O2 system, a protocol was developed that gave the desired β‐O‐4‐containing ester in high yield using certain dimeric model compounds. The optimised reaction conditions were then applied to an oligomeric lignin model system. Extensive 2D NMR analysis demonstrated that analogous chemistry could be achieved with the oligomeric substrate. Mild depolymerisation of the ester‐containing oligomer delivered the expected aryl acid monomer.
Comparative Study of the Supercapacitive Performance of Three Ferrocene‐Based Structures: Targeted Design of a Conductive Ferrocene‐Functionalized Coordination Polymer as a Supercapacitor Electrode
Authors: Miao Qian , Rouhani Farzaneh , Moghanni‐Bavil‐Olyaei Hamed , Liu Kuan‐Guan , Gao Xue‐Mei , Li Jing‐Zhe , Hu Xiu‐De , Jin Zhi‐Min , Hu Mao‐Lin , Morsali Ali
Published: May 2020

As redox‐active based supercapacitors are known as highly desirable next‐generation supercapacitor electrodes, the targeted design of two ferrocene‐functionalized (Fc(COOH)2) clusters based on coinage metals, [(PPh3)2AgO2CFcCO2Ag(PPh3)2]2⋅7 CH3OH (SC1: super capacitor) and [(PPh3)3CuO2CFcCO2Cu(PPh3)3]⋅3 CH3OH (SC2), is reported. Both structures are fully characterized by various techniques. The structures are utilized as energy storage electrode materials, giving 130 F g−1 and 210 F g−1 specific capacitance at 1.5 A g−1 in Na2SO4 electrolyte, respectively. The obtained results show that the presence of CuI instead of AgI improves the supercapacitive performance of the cluster. Further, to improve the conductivity, the PSC2 ([(PPh3)2CuO2CFcCO2]∞), a polymeric structure of SC2, was synthesized and used as an energy storage electrode. PSC2 displays high conductivity and gives 455 F g−1 capacitance at 3 A g−1. The PSC2 as a supercapacitor electrode presents a high power density (2416 W kg−1), high energy density (161 Wh kg−1), and long cycle life over 4000 cycles (93 %). These results could lead to the amplification of high‐performance supercapacitors in new areas to develop real applications and stimulate the use of the targeted design of coordination polymers without hybridization or compositions with additive materials.
Balancing Ligand Flexibility versus Rigidity for the Stepwise Self‐Assembly of M12L24 via M6L12 Metal–Organic Cages
Authors: Liu Cui‐Lian , Bobylev Eduard O. , Fu Yang , Poole David A. , Robeyns Koen , Fustin Charles‐André , Garcia Yann , Reek Joost N. H. , Singleton Michael L.
Published: May 2020

Non‐covalent interactions are important for directing protein folding across multiple intermediates and can even provide access to multiple stable structures with different properties and functions. Herein, we describe an approach for mimicking this behavior in the self‐assembly of metal–organic cages. Two ligands, the bend angles of which are controlled by non‐covalent interactions and one ligand lacking the above‐mentioned interactions, were synthesized and used for self‐assembly with Pd2+. As these weak interactions are easily broken, the bend angles have a controlled flexibility giving access to M2(L1)4, M6(L2)12, and M12(L2)24 cages. By controlling the self‐assembly conditions this process can be directed in a stepwise fashion. Additionally, the multiple endohedral hydrogen‐bonding sites on the ligand were found to play a role in the binding and discrimination of neutral guests.
Mechanism of an Elusive Solvent Effect in Organozinc Reagent Synthesis
Authors: Hanada Erin M. , Jess Kristof , Blum Suzanne A.
Published: May 2020

Solvent effects are often difficult to understand in cases where reaction intermediates, and thus their differential behavior in different solvents, are not directly observable by traditional ensemble analytical techniques. Herein, the sensitivity of single‐particle fluorescence microscopy uniquely enables direct observation of organozinc intermediates and solvent effects on their build‐up and persistence. When combined with NMR spectroscopy, these imaging data pinpoint the previously elusive mechanistic origin of solvent effects in the synthesis of widely used organozinc reagents. These findings characterize the acceleration of oxidative addition of the starting organoiodide to the surface of zinc metal in DMSO relative to THF, but once formed, surface intermediates display similar persistence in either solvent. The current studies are the first demonstration of a highly sensitive, single‐particle fluorescence microscopy technique to pinpoint otherwise elusive solvent effects in synthetic chemistry.
Switching warfarin to direct oral anticoagulants in atrial fibrillation: Insights from the NCDR PINNACLE registry
Authors: Sciria Christopher T. , Maddox Thomas M. , Marzec Lucas , Rodwin Benjamin , Virani Salim S. , Annapureddy Amarnath , Freeman James V. , O'Hare Ali , Liu Yuyin , Song Yang , Doros Gheorghe , Zheng Yue , Lee Jane J. , Daggubati Ramesh , Vadlamani Lina , Cannon Christopher , Desai Nihar R.
Published: May 2020

Background

Previous studies examining the use of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) have largely focused on patients newly initiating therapy. Little is known about the prevalence/patterns of switching to DOACs among AF patients initially treated with warfarin.

Hypothesis

To examine patterns of anticoagulation among patients chronically managed with warfarin upon the availability of DOACs and identify patient/practice‐level factors associated with switching from chronic warfarin therapy to a DOAC.

Methods

Prospective cohort study of AF patients in the NCDR PINNACLE registry prescribed warfarin between May 1, 2008 and May 1, 2015. Patients were followed at least 1 year (median length of follow‐up 375 days, IQR 154‐375) through May 1, 2016 and stratified as follows: continued warfarin, switched to DOAC, or discontinued anticoagulation. To identify significant predictors of switching, a three‐level multivariable hierarchical regression was developed.

Results

Among 383 008 AF patients initially prescribed warfarin, 16.3% (n = 62 620) switched to DOACs, 68.8% (n = 263 609) continued warfarin, and 14.8% (n = 56 779) discontinued anticoagulation. Among those switched, 37.6% received dabigatran, 37.0% rivaroxaban, 24.4% apixaban, and 1.0% edoxaban. Switched patients were more likely to be younger, women, white, and have private insurance (all P < .001). Switching was less likely with increased stroke risk (OR, 0.92; 95%CI, 0.91‐0.93 per 1‐point increase CHA2DS2‐VASc), but more likely with increased bleeding risk (OR, 1.12; 95%CI, 1.10‐1.13 per 1‐point increase HAS‐BLED). There was substantial variation at the practice‐level (MOR, 2.33; 95%CI, 2.12‐2.58) and among providers within the same practice (MOR, 1.46; 95%CI, 1.43‐1.49).

Conclusions

Among AF patients treated with warfarin between October 1, 2010 and May 1, 2016, one in six were switched to DOACs, with differences across sociodemographic/clinical characteristics and substantial practice‐level variation. In the context of current guidelines which favor DOACs over warfarin, these findings help benchmark performance and identify areas of improvement.