bluuebunny/crossref_metadata_2025 huggingface dataset:
BRCA1/Trp53
heterozygosity and replication stress drive esophageal cancer development in a mouse model
Authors: He Ye , Rivera Joshua , Diossy Miklos , Duan Haohui , Bowman-Colin Christian , Reed Rachel , Jennings Rebecca , Novak Jesse , Tran Stevenson V. , Cohen Elizabeth F. , Szuts David , Giobbie-Hurder Anita , Bronson Roderick T. , Bass Adam J. , Signoretti Sabina , Szallasi Zoltan , Livingston David M. , Pathania Shailja
Published: October 2021

Significance

Although germline heterozygous
BRCA1
mutations predispose human carriers to cancer, heterozygous mouse
BRCA1
mutations do not. We find that exposure to a source of upper gastrointestinal replication stress (RS) elicited a marked cancer incidence in
Brca1

+/−

;Trp53

+/−

heterozygous mice but not in wild-type mice (
Brca1

+/+

;Trp53

+/−

). Oral delivery of 4 nitroquinoline-1-oxide induced esophageal epithelial RS, an increased esophageal mutation rate, loss of esophageal
Brca1
heterozygosity (LOH), and accelerated esophageal tumorigenesis. These data underscore the necessity of combining otherwise nontumorigenic
BRCA1
heterozygosity with simultaneous induction of RS for the generation of not only
BRCA1
mutant esophageal cancer, but also a dramatically accelerated form thereof. These results strongly imply that RS is both a major contributor to
BRCA1
cancer development and a marked accelerant thereof.
Asymmetric protonation of glutamate residues drives a preferred transport pathway in EmrE
Authors: Li Jianping , Sae Her Ampon , Traaseth Nathaniel J.
Published: October 2021

Significance

EmrE is a proton-coupled efflux pump that confers multidrug resistance to
Escherichia coli
. Here, we probed the electrostatic environment surrounding each essential Glu14 residue in the EmrE dimer by determining monomer specific p
K

a

values using NMR spectroscopy. We discovered that acid/base chemistry at one of the two Glu14 residues in the homodimer potentiates a global conformational change within EmrE. Our findings revealed that asymmetric protonation states of EmrE leads to a preferred pathway of substrate transport. These insights led to a model to explain how EmrE accomplishes proton-coupled transport without leaking protons. Since the overall structure of EmrE resembles those of other transporters containing inverted repeat domains, our findings have application to other secondary active transporters.
Phospholipase Cγ2 regulates endocannabinoid and eicosanoid networks in innate immune cells
Authors: Jing Hui , Reed Alex , Ulanovskaya Olesya A. , Grigoleit Jan-Sebastian , Herbst Dylan M. , Henry Cassandra L. , Li Haoxin , Barbas Sabrina , Germain Jason , Masuda Kim , Cravatt Benjamin F.
Published: October 2021

Significance

Here, we reveal that activation of phospholipase Cγ2 (PLCγ2) by disease-relevant mutations or Fc receptor signaling stimulates the production of the endocannabinoid 2-arachidonylglycerol and prostaglandins in primary human and mouse immune cells through a pathway that involves the DAG lipase (DAGL) and monoacylglycerol lipase (MGLL) enzymes.
Plcg2
deficiency suppressed DAGL/MGLL-mediated endocannabinoid-eicosanoid cross-talk in mouse microglia, leading to impairment in lipopolysaccharide-mediated microglia activation in vivo that included reduced prostaglandin production and CD68 expression. Our studies provide important mechanistic insights into the regulation of lipid signaling pathways in primary immune cells, revealing a PLCγ2-DAGL-MGLL network that may serve as a future target for treating diverse immunopathologies.
Developing an index of sustainable development goals for local governments: the case of Gyeonggi province in korea
Authors: Koh Jaekyung , Huh Taewook , Ye Minji
Published: October 2021

This study aims to develop and evaluate the indicators of Sustainable Development Goals (hereafter SDGs) for local governments in Gyeonggi Province, South Korea from the perspective of the glocal mainstreaming of SDGs and localization. Through surveys and focus group meetings, 35 SDGs indicators that are to be implemented by both the Gyeonggi Provincial government and 31 separate local governments were selected and an overall index was calculated by standardizing 27 indicators. Through the comparative analysis of the fuzzy-set, this paper revealed the four ideal types along with the arrangement of two variables, the socio-economic SDGs index (S) and the environmental SDGs index (E), which are derived from 31 local governments. In short, some examples of this arrangement are the Type 1 (S*E: “sustainable local gov.”) including Hanam City (fuzzy score, 0.729); Type 2 (S*e: “imbalanced local gov.(I)”) including Hwaseong City (0.862); Type 3 (s*E: “imbalanced local gov.(II)”) including Gapyeong County (0.922); and Type 4 (s*e: “unsustainable local gov.”) including Pyeongtaek City (0.650). As a result, this paper suggests policy priority should be placed on the local governments of Type 4 where all three dimensions of sustainable development pose challenges. Furthermore, it is important for Type 2 and Type 3 to enhance policy coherence for sustainability.
The pathophysiology of sepsis—2021 update: Part 1, immunology and coagulopathy leading to endothelial injury
Authors: Jacobi Judith
Published: October 2021

Purpose

To provide an overview of current literature on the pathophysiology of sepsis, with a focus on mediators of endothelial injury and organ dysfunction.

Sepsis is a dysregulated response to infection that triggers cascades of interconnected systems. Sepsis has been a significant cause of mortality worldwide, and the recent viral pandemic that may produce severe sepsis and septic shock has been a major contributor to sepsis-related mortality. Understanding of the pathophysiology of sepsis has changed dramatically over the last several decades. Significant insight into the components of the inflammatory response that contribute to endothelial injury and trigger coagulation pathways has been achieved. Similarly, characterization of anti-inflammatory pathways that may lead to secondary infections and poor outcome has illustrated opportunities for improved therapies. Description of an increasing number of important mediators and pathways has occurred and may point the way to novel therapies to address immune dysregulation. Pharmacists will need a fundamental understanding of the overlapping pathways of the immune response to fully prepare for use of novel treatment options. While pharmacists typically understand coagulation cascade how to utilize anticoagulants, the issues in sepsis related coagulopathy and role of mediators such as cytokines and complement and role of activated platelets and neutrophils require a different perspective.

Conclusion

Pharmacists can benefit from understanding both the cellular and organ system issues in sepsis to facilitate assessment of potential therapies for risk and benefit.
Galaxy Is a Suitable Bioinformatics Platform for the Molecular Diagnosis of Human Genetic Disorders Using High-Throughput Sequencing Data Analysis: Five Years of Experience in a Clinical Laboratory
Authors: Chappell Kenneth , Francou Bruno , Habib Christophe , Huby Thomas , Leoni Marco , Cottin Aurélien , Nadal Florian , Adnet Eric , Paoli Eric , Oliveira Christophe , Verstuyft Céline , Davit-Spraul Anne , Gaignard Pauline , Lebigot Elise , Duclos-Vallee Jean-Charles , Young Jacques , Kamenicky Peter , Adams David , Echaniz-Laguna Andoni , Gonzales Emmanuel , Bouvattier Claire , Linglart Agnes , Picard Véronique , Bergoin Emilie , Jacquemin Emmanuel , Guiochon-Mantel Anne , Proust Alexis , Bouligand Jérôme
Published: October 2021

Background

To date, the usage of Galaxy, an open-source bioinformatics platform, has been reported primarily in research. We report 5 years’ experience (2015 to 2020) with Galaxy in our hospital, as part of the “Assistance Publique–Hôpitaux de Paris” (AP-HP), to demonstrate its suitability for high-throughput sequencing (HTS) data analysis in a clinical laboratory setting.

Methods

Our Galaxy instance has been running since July 2015 and is used daily to study inherited diseases, cancer, and microbiology. For the molecular diagnosis of hereditary diseases, 6970 patients were analyzed with Galaxy (corresponding to a total of 7029 analyses).

Results

Using Galaxy, the time to process a batch of 23 samples—equivalent to a targeted DNA sequencing MiSeq run—from raw data to an annotated variant call file was generally less than 2 h for panels between 1 and 500 kb. Over 5 years, we only restarted the server twice for hardware maintenance and did not experience any significant troubles, demonstrating the robustness of our Galaxy installation in conjunction with HTCondor as a job scheduler and a PostgreSQL database. The quality of our targeted exome sequencing method was externally evaluated annually by the European Molecular Genetics Quality Network (EMQN). Sensitivity was mean (SD)% 99 (2)% for single nucleotide variants and 93 (9)% for small insertion-deletions.

Conclusion

Our experience with Galaxy demonstrates it to be a suitable platform for HTS data analysis with vast potential to benefit patient care in a clinical laboratory setting.
Feasibility and optimal operation of micro energy hybrid system (hydro/wind) in the rural valley region
Authors: Kefif Nesrine , Melzi Bachir , Hashemian Mehran , Assad Mamdouh El Haj , Hoseinzadeh Siamak
Published: October 2021

With the increase in the global and local demand for electrical energy, which is necessary for the functioning of several fields such as the economy and agriculture, this study introduces a micro-hydro–wind hybrid system in order to obtain an economic feasibility of the off-grid isolated and renewable energy system. The main objective of this research is to determine the optimum design size for a hydro–wind hybrid energy system that is supposed to meet the demand for the electric load in front of a valley in Algeria called Yesser with variable water flow and wind speeds in three positions. Batteries are supplied to increase the reliability of the system when the performance of the wind turbine energy and the flow rate of the hydro system are evaluated. This system is proposed to reduce financial costs in addition to the possibility of providing interchangeable energy and operating reserves with short start times. The Homer Pro software is used to model the hybrid renewable energy system and to perform the required analysis of the economic side of the system in terms of the valley's flow rate and the wind speed. The average speed of the water flow in Yesser valley is varied between 10 and 24.6 m3/s, and three cases of the valley's flow rate were studied with the maximum and minimum wind speeds: the passage (the transit) with 10 m3/s, the downstream (the estuary) with 19 m3/s and the valley's upstream (the source) with 24.6 m3/s. From the results, it appears that the hydro power was not enough to meet the load demand in the first area (the transit); however, the hydro/wind hybrid system was capable to feed the required load. For the second area (the estuary) the wind power was needed just in summer season, and for the third area (the source) the hydro generator was sufficient to feed the load all the year as the hydro power generated exceeds the load demand. The Homer Pro software calculations prove that the financial cost of the system is inversely proportional with the wind speed, such that the higher the wind speed the lower the cost of the system, the same relationship is for the flow rate speed as we consider the third case the most cost-effective with 61 330.46 USD.
Superoxide Dismutase, BDNF, and Cognitive Improvement in Drug-Naive First-Episode Patients With Schizophrenia: A 12-Week Longitudinal Study
Authors: Wu Zhiwei , Liu Qinqin , Zhang Yinghua , Guan Xiaoni , Xiu Meihong , Zhang Xiangyang
Published: October 2021

Objective

Cognitive improvement after antipsychotic agents in patients with schizophrenia (SCZ) appears to involve redox regulation through neurotrophins such as brain derived neurotropic factor (BDNF). This study examined whether cognitive improvement was associated with the increase in superoxide dismutase (SOD) and whether higher levels of BDNF could have a permissive role in allowing SOD to improve cognition.

Methods

We examined this hypothesis in 183 drug-naïve first-episode SCZ patients taking risperidone monotherapy for 12 weeks. We measured total copper-zinc SOD (CuZn-SOD), manganese SOD (Mn-SOD), and SOD activities and BDNF levels in these patients and compared their levels with 152 healthy controls. We assessed cognitive functioning and clinical symptoms at baseline and 12-week follow-up.

Results

After treatment with risperidone, CuZn-SOD activity was significantly increased, and BDNF levels were slightly increased. Increased CuZn-SOD activity was associated with the cognitive effectiveness of risperidone monotherapy. The BDNF levels and SOD activities were correlated at baseline but not after 12-week treatment. Furthermore, baseline CuZn-SOD activity positively correlated with improvement on the delayed memory subscale of the Repeatable Battery for the Assessment of Neuropsychological Status only in the high BDNF subgroup.

Conclusions

Our longitudinal study suggests that risperidone can enhance SOD activity and that, in combination with higher baseline BDNF levels acting in a permissive role, can improve cognitive impairments in SCZ. Greater baseline CuZn-SOD activity also may have predictive value for cognitive improvement of delayed memory in SCZ patients receiving risperidone treatment.
Sections of Convex Bodies in John’s and Minimal Surface Area Position
Authors: Alonso-Gutiérrez David , Brazitikos Silouanos
Published: October 2021

We prove several estimates for the volume, the mean width, and the value of the Wills functional of sections of convex bodies in John’s position, as well as for their polar bodies. These estimates extend some well-known results for convex bodies in John’s position to the case of lower-dimensional sections, which had mainly been studied for the cube and the regular simplex. Some estimates for centrally symmetric convex bodies in minimal surface area position are also obtained.
Fecal Shedding of 2 Novel Live Attenuated Oral Poliovirus Type 2 Vaccine Candidates by Healthy Infants Administered Bivalent Oral Poliovirus Vaccine/Inactivated Poliovirus Vaccine: 2 Randomized Clinical Trials
Authors: Gast Christopher , Bandyopadhyay Ananda S , Sáez-Llorens Xavier , De Leon Tirza , DeAntonio Rodrigo , Jimeno José , Aguirre Gabriela , McDuffie Larin M , Coffee Elizabeth , Mathis Demetrius L , Oberste M Steven , Weldon William C , Konopka-Anstadt Jennifer L , Modlin John , Bachtiar Novilia S , Fix Alan , Konz John , Clemens Ralf , Costa Clemens Sue Ann , Rüttimann Ricardo
Published: October 2021

Background

Primary intestinal immunity through viral replication of live oral vaccine is key to interrupt poliovirus transmission. We assessed viral fecal shedding from infants administered Sabin monovalent poliovirus type 2 vaccine (mOPV2) or low and high doses of 2 novel OPV2 (nOPV2) vaccine candidates.

Methods

In 2 randomized clinical trials in Panama, a control mOPV2 study (October 2015 to April 2016) and nOPV2 study (September 2018 to October 2019), 18-week-old infants vaccinated with bivalent oral poliovirus vaccine/inactivated poliovirus vaccine received 1 or 2 study vaccinations 28 days apart. Stools were assessed for poliovirus RNA by polymerase chain reaction (PCR) and live virus by culture for 28 days postvaccination.

Results

Shedding data were available from 621 initially reverse-transcription PCR–negative infants (91 mOPV2, 265 nOPV2-c1, 265 nOPV2-c2 recipients). Seven days after dose 1, 64.3% of mOPV2 recipients and 31.3%–48.5% of nOPV2 recipients across groups shed infectious type 2 virus. Respective rates 7 days after dose 2 decreased to 33.3% and 12.9%–22.7%, showing induction of intestinal immunity. Shedding of both nOPV2 candidates ceased at similar or faster rates than mOPV2.

Conclusions

Viral shedding of either nOPV candidate was similar or decreased relative to mOPV2, and all vaccines showed indications that the vaccine virus was replicating sufficiently to induce primary intestinal mucosal immunity.
Health Technology Assessment (HTA) evidence, regulatory classification and reimbursement of medicine: the case of glucosamine
Authors: Luksameesate Parnnaphat , Taychakhoonavudh Suthira
Published: October 2021

Objectives

To examine the relationship among Health Technology Assessment (HTA) evidence, regulatory classification and reimbursement of health products using glucosamine as a case study. Data of HTA evidence, regulatory classification and reimbursement of glucosamine from 13 countries were extracted from official government websites and peer-reviewed journal articles. Role and responsibility of HTA in each country along as well as the regulatory approval process and reimbursement status of health products were reviewed. The case of glucosamine was then analysed to explore the regulatory classification, reimbursement and its HTA evidence from past to present.

Key findings

For regulatory classification, we found that glucosamine is classified as either medicine (9 from 13 countries) or a dietary supplement (4 from 13 countries) depends on where glucosamine is seeking its market approval. Reimbursement also differs among the countries. We summarized the key factors that could be the cause of these variations. First, the clinical evidence of glucosamine is still in question especially its efficacy and as a results its cost-effectiveness. This evidence is important for policy consideration. Secondly, different level of HTA approach in each healthcare system and country context effect on how HTA evidence is utilized and synthesized. Lastly, company’s strategic positioning is the first key stakeholder to decide whether their product would be registered as medicine or dietary supplement.

The variation of HTA evidence in a diverse healthcare system affects regulatory classifications and reimbursement. This can result in different levels of patient access to health products.
Measurement of the anisotropy power spectrum of the radio synchrotron background
Authors: Offringa A R , Singal J , Heston S , Horiuchi S , Lucero D M
Published: October 2021

We present the first targeted measurement of the power spectrum of anisotropies of the radio synchrotron background, at 140 MHz, where it is the overwhelmingly dominant photon background. This measurement is important for understanding the background level of radio sky brightness, which is dominated by steep-spectrum synchrotron radiation at frequencies below ν ∼ 0.5 GHz and has been measured to be significantly higher than that produced by known classes of extragalactic sources and most models of Galactic halo emission. We determine the anisotropy power spectrum on scales ranging from 2° to 0.2 arcmin with Low-Frequency Array observations of two 18-deg2 fields – one centred on the Northern hemisphere’s coldest patch of radio sky where the Galactic contribution is smallest and the other offset from that location by 15°. We find that the anisotropy power is higher than that attributable to the distribution of point sources above 100 $\mu$Jy in flux. This level of radio anisotropy power indicates that if it results from point sources, those sources are likely at low fluxes and incredibly numerous, and likely clustered in a specific manner.
Genotoxicity of advanced glycation end products in vitro is influenced by their preparation temperature, purification and cell exposure time
Authors: Jaunay Emma L , Dhillon Varinderpal S , Semple Susan J , Simpson Bradley S , Ghetia Maulik , Deo Permal , Fenech Michael
Published: October 2021

Advanced glycation end products (AGEs) are formed via non-enzymatic reactions between amino groups of proteins and the carbonyl groups of reducing sugars. Previous studies have shown that highly glycated albumin prepared using a glucose-bovine serum albumin (Glu-BSA) model system incubated at 60°C for 6 weeks induces genotoxicity in WIL2-NS cells at 9 days of exposure measured by the cytokinesis-block micronucleus cytome (CBMNcyt) assay. However, this AGE model system is not physiologically relevant as normal body temperature is 37°C and the degree of glycation may exceed the extent of albumin modification in vivo. We hypothesised that the incubation temperature and purification method used in these studies may cause changes to the chemical profile of the glycated albumin and may influence the extent of genotoxicity observed at 3, 6 and 9 days of exposure. We prepared AGEs generated using Glu-BSA model systems incubated at 60°C or 37°C purified using trichloroacetic acid (TCA) precipitation or ultrafiltration (UF) and compared their chemical profile (glycation, oxidation, and aggregation) and genotoxicity in WIL2-NS cells using the CBMNcyt assay after 3, 6 and 9 days of exposure. The number of micronuclei (MNi) was significantly higher for cells treated with Glu-BSA incubated at 60°C and purified via TCA (12 ± 1 MNi/1000 binucleated cells) compared to Glu-BSA incubated at 37°C and purified using UF (6 ± 1 MNi/1000 binucleated cells) after 9 days (P < 0.0001). The increase in genotoxicity observed could be explained by a higher level of protein glycation, oxidation, and aggregation of the Glu-BSA model system incubated at 60°C relative to 37°C. This study highlighted that the incubation temperature, purification method and cell exposure time are important variables to consider when generating AGEs in vitro and will enable future studies to better reflect in vivo situations of albumin glycation.
The Natural Products Atlas 2.0: a database of microbially-derived natural products
Authors: van Santen Jeffrey A , Poynton Ella F , Iskakova Dasha , McMann Emily , Alsup Tyler A , Clark Trevor N , Fergusson Claire H , Fewer David P , Hughes Alison H , McCadden Caitlin A , Parra Jonathan , Soldatou Sylvia , Rudolf Jeffrey D , Janssen Elisabeth M-L , Duncan Katherine R , Linington Roger G
Published: October 2021

Within the natural products field there is an increasing emphasis on the study of compounds from microbial sources. This has been fuelled by interest in the central role that microorganisms play in mediating both interspecies interactions and host-microbe relationships. To support the study of natural products chemistry produced by microorganisms we released the Natural Products Atlas, a database of known microbial natural products structures, in 2019. This paper reports the release of a new version of the database which includes a full RESTful application programming interface (API), a new website framework, and an expanded database that includes 8128 new compounds, bringing the total to 32 552. In addition to these structural and content changes we have added full taxonomic descriptions for all microbial taxa and have added chemical ontology terms from both NP Classifier and ClassyFire. We have also performed manual curation to review all entries with incomplete configurational assignments and have integrated data from external resources, including CyanoMetDB. Finally, we have improved the user experience by updating the Overview dashboard and creating a dashboard for taxonomic origin. The database can be accessed via the new interactive website at https://www.npatlas.org.
PCMDB: a curated and comprehensive resource of plant cell markers
Authors: Jin Jingjing , Lu Peng , Xu Yalong , Tao Jiemeng , Li Zefeng , Wang Shuaibin , Yu Shizhou , Wang Chen , Xie Xiaodong , Gao Junping , Chen Qiansi , Wang Lin , Pu Wenxuan , Cao Peijian
Published: October 2021

The advent of single-cell sequencing opened a new era in transcriptomic and genomic research. To understand cell composition using single-cell studies, a variety of cell markers have been widely used to label individual cell types. However, the specific database of cell markers for use by the plant research community remains very limited. To overcome this problem, we developed the Plant Cell Marker DataBase (PCMDB, http://www.tobaccodb.org/pcmdb/), which is based on a uniform annotation pipeline. By manually curating over 130 000 research publications, we collected a total of 81 117 cell marker genes of 263 cell types in 22 tissues across six plant species. Tissue- and cell-specific expression patterns can be visualized using multiple tools: eFP Browser, Bar, and UMAP/TSNE graph. The PCMDB also supports several analysis tools, including SCSA and SingleR, which allows for user annotation of cell types. To provide information about plant species currently unsupported in PCMDB, potential marker genes for other plant species can be searched based on homology with the supported species. PCMDB is a user-friendly hierarchical platform that contains five built-in search engines. We believe PCMDB will constitute a useful resource for researchers working on cell type annotation and the prediction of the biological function of individual cells.
G4LDB 2.2: a database for discovering and studying G-quadruplex and i-Motif ligands
Authors: Wang Yu-Huan , Yang Qian-Fan , Lin Xiao , Chen Die , Wang Zhi-Yin , Chen Bin , Han Hua-Yi , Chen Hao-Di , Cai Kai-Cong , Li Qian , Yang Shu , Tang Ya-Lin , Li Feng
Published: October 2021

Noncanonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have attracted increasing research interests because of their unique structural and binding properties, as well as their important biological activities. To date, thousands of small molecules that bind to varying G4/iM structures have been designed, synthesized and tested for diverse chemical and biological uses. Because of the huge potential and increasing research interests on G4-targeting ligands, we launched the first G4 ligand database G4LDB in 2013. Here, we report a new version, termed G4LDB 2.2 (http://www.g4ldb.com), with upgrades in both content and function. Currently, G4LDB2.2 contains >3200 G4/iM ligands, ∼28 500 activity entries and 79 G4–ligand docking models. In addition to G4 ligand library, we have also added a brand new iM ligand library to G4LDB 2.2, providing a comprehensive view of quadruplex nucleic acids. To further enhance user experience, we have also redesigned the user interface and optimized the database structure and retrieval mechanism. With these improvements, we anticipate that G4LDB 2.2 will serve as a comprehensive resource and useful research toolkit for researchers across wide scientific communities and accelerate discovering and validating better binders and drug candidates.
Precision of measurements and the biases due to the geomagnetic declination in the Korean observations of the comet C/1723 T1
Authors: Ahn Sang-Hyeon
Published: October 2021

Positions of the comet C/1723 T1 recorded in Korean historical resources are analysed to estimate the precision of measurements and the bias due to the geomagnetic declination at Seoul. We calculate the ephemeris of the comet by adopting the orbital elements determined by Gustav Spörer in 1843 based upon the Bradley’s telescopic observations in 1723. We confirm that the Bradley’s observations have a measurement error of 25″. The positions of the comet recorded in the Korean manuscripts are compared with the modern ephemeris. We find that there are misalignments in the instrument’s polar axis with Earth’s rotation axis: if the measurements were rounded up, there are alignment errors of 0.°0 ± 0.°2 in elevation and $-{0{_{.}^{\circ}}3}\pm {0{_{.}^{\circ}}3}$ in azimuth (to 1σ); if the measurements were rounded down, there are alignment errors of −0.°5 ± 0.°4 in elevation and +0.°5 ± 0.°6 in azimuth (to 1σ). Assuming that the instrument’s polar axis was aligned with a magnetic compass, we can regard the misalignment of the polar axis in azimuth as the geomagnetic declination at Seoul in 1723. We find that the geomagnetic declination obtained is in agreement with the recent models of the historical geomagnetic fields. We also obtain the one-time measurement error of ${0{_{.}^{\circ}}25}$, which is not different from the one-time measurement error of ${0{_{.}^{\circ}}3}$ obtained from the observational data of Mars in 1491.
The efficacy and safety of intermittent preventive treatment with sulphadoxine-pyrimethamine vs artemisinin-based drugs for malaria: a systematic review and meta-analysis
Authors: Chu Xiajing , Yan Peijing , Zhang Na , Chen Nan , Liu Yang , Feng Lufang , Li Meixuan , Zhang Ziyao , Wang Qi , Wang Shizhong , Yang Kehu
Published: October 2021

Background

Malaria is one of the most serious global problems. The objective of this study is to assess whether intermittent preventive treatment (IPT) using artemisinin-based combination therapies (ACTs) was a promising alternative to IPT with sulphadoxine-pyrimethamine (IPT-SP).

Methods

We searched the following sources up to 12 August 2020: PubMed, The Cochrane Library, Embase, Web of Science, CNKI, CBM, VIP and WanFang Database from inception. The randomized controlled trials comparing SP with ACTs for malaria were included. Data were pooled using Stata.14 software. We performed subgroup analysis based on the different types of ACTs groups and participants.

Results

A total of 13 studies comprising 5180 people were included. The meta-analysis showed that ACTs had the lower risk of number of any parasitemia (RR=0.46; 95% CI 0.22 to 0.96, p=0.039; I2=90.50%, p<0.001), early treatment failure (RR=0.17; 95% CI 0.06 to 0.48, p<0.001; I2=66.60%, p=0.011) and late treatment failure (RR=0.34; 95% CI 0.13 to 0.92, p<0.001; I2=87.80%, p<0.001) compared with SP. There was no significant difference in adequate clinical response, average hemoglobin and adverse neonatal outcomes.

Conclusion

Combinations with ACTs appear promising as suitable alternatives for IPT-SP.
Transmission and Pathogenicity of Papaya Virus E: Insights from an Experimental Papaya Orchard
Authors: Cornejo-Franco Juan F. , Reyes-Proaño Edison , Mollov Dimitre , Mowery Joseph , Quito-Avila Diego F.
Published: October 2021

A study was conducted to investigate epidemiological aspects of papaya virus E (PpVE), a cytorhabdovirus commonly found in papaya (Carica papaya L.) plantings in Ecuador. Besides papaya, PpVE was found in three Fabaceae weeds, including Rhynchosia minima, Centrosema plumieri, and Macroptilium lathyroides, the latter being the species with the highest virus prevalence. Greenhouse experiments showed that in M. lathyroides, single infections of PpVE induce only mild leaf mosaic, whereas in mixed infections with cowpea severe mosaic virus, PpVE contributes to severe mosaic. In papaya, PpVE did not induce noticeable symptoms in single or mixed infections with papaya ringspot virus. Transmission experiments confirmed that whiteflies (Bemisia tabaci) transmit PpVE in a semipersistent, nonpropagative manner.
Association Between Vasopressin Rebranding and Utilization in Patients With Septic Shock*
Authors: Sacha Gretchen L. , Kiser Tyree H. , Wright Garth C. , Vandivier R. William , Moss Marc , Burnham Ellen L. , Ho P. Michael , Reynolds Paul M. , Bauer Seth R.
Published: October 2021

OBJECTIVES:

Vasopressin is suggested as an adjunct to norepinephrine in patients with septic shock. However, after vasopressin was rebranded in November 2014, its cost exponentially increased. Utilization patterns of vasopressin after its rebranding are unclear. The objective of this study was to determine if there is an association between the rebranding of vasopressin in November 2014 and its utilization in vasopressor-dependent patients with severe sepsis or septic shock.

DESIGN:

Retrospective, multicenter, database study between January 2010 and March 2017.

SETTING:

Premier Healthcare Database hospitals.

PATIENTS:

Adult patients admitted to an ICU with severe sepsis or septic shock, who received at least one vasoactive agent for two or more calendar days were included.

INTERVENTIONS:

The proportion of patients who received vasopressin and vasopressin cost was assessed before and after rebranding, and evaluated with segmented regression.

MEASUREMENTS AND MAIN RESULTS:

Among 294,733 patients (mean age, 66 ± 15 yr), 27.8% received vasopressin, and ICU mortality was 26.5%. The proportion of patients receiving vasopressin was higher after rebranding (31.2% postrebranding vs 25.8% prerebranding). Before vasopressin rebranding, the quarterly proportion of patients who received vasopressin had an increasing slope (prerebranding slope 0.41% [95% CI, 0.35–0.46%]), with no difference in slope detected after vasopressin rebranding (postrebranding slope, 0.47% [95% CI, 0.29–0.64%]). After vasopressin rebranding, mean vasopressin cost per patient was higher ($527 ± 1,130 vs $77 ± 160), and the quarterly slope of vasopressin cost was higher (change in slope $77.18 [95% CI, $75.73–78.61]). Total vasopressin billed cost postrebranding continually increased by ~$294,276 per quarter from less than $500,000 in Q4 2014 to over $3,000,000 in Q1 2017.

CONCLUSIONS:

After vasopressin rebranding, utilization continued to increase quarterly despite a significant increase in vasopressin cost. Vasopressin appeared to have price inelastic demand in septic shock.
Coronavirus Disease 2019 and Out-of-Hospital Cardiac Arrest: No Survivors*
Authors: Baert Valentine , Beuscart Jean-Baptiste , Recher Morgan , Javaudin François , Hugenschmitt Delphine , Bony Thomas , Revaux François , Mansouri Nadia , Larcher Fanny , Chazard Emmanuel , Hubert Hervé
Published: October 2021

OBJECTIVES:

To describe and compare survival among patients with out-of-hospital cardiac arrest as a function of their status for coronavirus disease 2019.

DESIGN:

We performed an observational study of out-of-hospital cardiac arrest patients between March 2020 and December 2020. Coronavirus disease 2019 status (confirmed, suspected, or negative) was defined according to the World Health Organization’s criteria.

SETTING:

Information on the patients and their care was extracted from the French national out-of-hospital cardiac arrest registry. The French prehospital emergency medical system has two tiers: the fire department intervenes rapidly to provide basic life support, and mobile ICUs provide advanced life support. The study data (including each patient’s coronavirus disease 2019 status) were collected by 95 mobile ICUs throughout France.

PATIENTS:

We included 6,624 out-of-hospital cardiac arrest patients: 127 cases with confirmed coronavirus disease 2019, 473 with suspected coronavirus disease 2019, and 6,024 negative for coronavirus disease 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The “confirmed” and “suspected” groups of coronavirus disease 2019 patients had similar characteristics and were more likely to have suffered an out-of-hospital cardiac arrest with a respiratory cause (confirmed: 53.7%, suspected coronavirus disease 2019: 56.5%; p = 0.472) than noncoronavirus disease 2019 patients (14.0%; p < 0.001 vs confirmed coronavirus disease 2019 patients). Advanced life support was initiated for 57.5% of the confirmed coronavirus disease 2019 patients, compared with 64.5% of the suspected coronavirus disease 2019 patients (p = 0.149) and 70.6% of the noncoronavirus disease 2019 ones (p = 0.002). The survival rate at 30-day postout-of-hospital cardiac arrest was 0% in the confirmed coronavirus disease 2019 group, 0.9% in the suspected coronavirus disease 2019 group (p = 0.583 vs confirmed), and 3.5% (p = 0.023) in the noncoronavirus disease 2019 group.

CONCLUSIONS:

Our results highlighted a zero survival rate in out-of-hospital cardiac arrest patients with confirmed coronavirus disease 2019. This finding raises important questions with regard to the futility of resuscitation for coronavirus disease 2019 patients and the management of the associated risks.
Urinary concentrations of phenols and parabens and incident diabetes in midlife women
Authors: Lee Seulbi , Karvonen-Gutierrez Carrie , Mukherjee Bhramar , Herman William H. , Harlow Siobán D. , Park Sung Kyun
Published: October 2021

Background:

Environmental phenols have been suggested as diabetogens but evidence from prospective cohort studies is limited. We examined associations between urinary concentrations of phenols and parabens, assessed at two time-points, and incident diabetes in the Study of Women’s Health Across the Nation (SWAN).

Methods:

We examined 1,299 women, aged 45–56 years, who were diabetes-free at baseline of the SWAN Multi-Pollutant Study (MPS) (1999–2000) and were followed through January 2017. Urinary concentrations of bisphenol-A, bisphenol-F, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, benzophenone-3, methyl-paraben, ethyl-paraben, propyl-paraben, and butyl-paraben were measured twice at MPS baseline and 3 years later (2002–2003), and the two average concentrations were used as exposure variables. Associations of incident diabetes with individual phenols and parabens were examined using Cox regression. We evaluated the overall joint effects using quantile-based g-computation.

Results:

Adjusted hazard ratios (HRs) for incident diabetes of the third tertile compared with the first tertile of urinary concentrations were 0.40 (95% confidence interval [CI] = 0.29, 0.56) for methyl-paraben; 0.42 (0.30, 0.58) for propyl-paraben; 0.53 (0.38, 0.75) for 2,5-diclrorophenol; and 0.55 (0.39, 0.80) for benzophenone-3. Nonlinear associations were found for bisphenol-A and 2,4-dichlorophenol (significant positive associations in the second tertile but no associations in the third tertile compared with the first tertile). No significant associations were observed for the other individual chemicals or the joint effect of mixtures.

Conclusions:

Our findings do not support diabetogenic effects of urinary parabens which were inversely associated with incident diabetes among mid-life women. Epidemiologic findings for biomarkers with short half-lives and high within-person variability need to be interpreted with caution.
Long-term Follow-up of Preoperative Infant Event-related Potentials in School-age Children with Craniosynostosis
Authors: Junn Alexandra , Dinis Jacob , Park Kitae E. , Hauc Sacha , Yang Jenny F. , Chuang Carolyn , Han Gloria , McPartland James C. , Persing John A. , Alperovich Michael
Published: October 2021

Background:

Previous studies demonstrated impaired auditory processing in children with sagittal and metopic craniosynostosis before surgical correction. This study investigated whether worse presurgical neural response as assessed by event-related potentials (ERP) was predictive of poorer school-age neurocognition.

Methods:

Preoperative infant ERP was recorded in 15 sagittal and 18 metopic patients. Mismatch negativity and P150 paradigms were derived from ERP recordings, as previously published. Of those, 13 sagittal and 13 metopic patients returned for neurocognitive evaluation 6 or more years later. ERP was correlated to neurocognitive outcomes using Spearman's correlations controlling for age. Two-tailed t-tests were used to evaluate the influence of age at the time of surgery (6 months) and morphologic severity on neurocognitive outcomes

Results:

In the sagittal group, no significant correlations were found between preoperative mismatch negativity or P150 amplitudes and neurocognitive outcomes. Although no correlation was found between mismatch negativity and neurocognitive outcome in the metopic group, those with lower P150 amplitudes had higher scores in performance IQ (r = −0.877, P < 0.001) and full-scale IQ (r = −0.893, P < 0.001). Morphologic severity and neurocognitive outcomes showed no relationship in the sagittal or metopic groups. Patients who received surgery at less than 6 months had higher full-scale IQ (109.69 versus 95.92, P = 0.025), visuomotor integration (103.15 versus 90.46, P = 0.041), and visual perception scores (105.69 versus 96.08, P = 0.033).

Conclusions:

Preoperative infant ERP does not correlate with school-age neurocognitive outcomes. Earlier age at the time of surgery was associated with improved neurocognitive outcomes.
Defining the Dimensions of Periosteal Free Tissue Transfer Harvest Sites
Authors: Hewitt Lyndel , Yabe Takako , Wykes James , McAndrew Darryl J. , Clark Jonathan R. , Ashford Bruce G.
Published: October 2021

Information about the use and donor site morbidity of periosteal free flaps in head and neck reconstruction is limited. The aim of this study was to examine potential periosteal free flap donor sites with respect to their dimensions, tissue and pedicle characteristics, and predicted donor site morbidity in a cadaveric model. The following cadaveric periosteal specimens with a vascular pedicle were harvested using standard surgical approaches: skull, chest wall, sternum, scapula, iliac crest, femur, and humerus. Data relating to the periosteum size and quality, vascular pedicle, surgical factors, feasibility of use, and the potential donor-site morbidity were recorded. One female (age: 78 years, height: 152 cm) and one male (age: 65 years, height: 186 cm) cadaver were used for flap harvest. The skull, chest wall, scapula, and femur were suitable in terms of the size of the periosteum harvested. The procedure to remove the periosteum from the scalp, chest wall, and scapula had the least predicted donor-site morbidity. The pedicle length and vessel caliber from the periosteal flaps were most favorable from the skull, scapula, and iliac crest. Considering all factors, the periosteum harvested from the skull and scapula were the most promising.
Clinical Nurse Specialist Practice
Authors: Burnie Jeannie , Vining Samantha
Published: October 2021

Purpose/Objectives

Blood culture collection is a common procedure performed in emergency departments. Rate of blood culture contamination is a metric that is tracked by organizations to ensure appropriate treatment for patients suspected of having bacteremia and ensure appropriate use of hospital resources. A team of nurses and technicians undertook a quality improvement project to decrease blood culture contamination rates in a suburban emergency department.

Description of the Project

The project included use of standardized blood culture collection kits, creation of a dedicated collection team, and implementation of a new blood culture collection device.

Outcome

Through this work, blood culture contamination rates decreased from greater than 3.0% to less than 1.5% consistently for nearly 24 months.

Conclusions

Providing feedback and continued monitoring has made this quality improvement initiative a success for the department and the organization and has resulted in cost savings of nearly 2 million dollars.
In vitro effectiveness of biapenem against IMP-producing Enterobacteriaceae
Authors: Gotoh Kazuyoshi , Miyoshi Makoto , Mayura I Putu Bayu , Iio Koji , Matsushita Osamu , Otsuka Fumio , Hagiya Hideharu
Published: October 2021

The options available for treating infections with carbapenemase-producing

Enterobacteriaceae

(CPE) are limited; with the increasing threat of these infections, new treatments are urgently needed. Biapenem (BIPM) is a carbapenem, and limited data confirming its in vitro killing effect against CPE are available. In this study, we examined the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of BIPM for 14 IMP-1-producing

Enterobacteriaceae

strains isolated from the Okayama region in Japan. The MICs against almost all the isolates were lower than 0.5 µg ml−1, indicating susceptibility to BIPM, while approximately half of the isolates were confirmed to be bacteriostatic to BIPM. However, initial killing to a 99.9 % reduction was observed in seven out of eight strains in a time–kill assay. Despite the small data set, we concluded that the in vitro efficacy of BIPM suggests that the drug could be a new therapeutic option against infection with IMP-producing CPE.
Comparative analysis of integrative and conjugative mobile genetic elements in the genus Mesorhizobium
Authors: Colombi Elena , Perry Benjamin J. , Sullivan John T. , Bekuma Amanuel A. , Terpolilli Jason J. , Ronson Clive W. , Ramsay Joshua P.
Published: October 2021

Members of the

Mesorhizobium

genus are soil bacteria that often form nitrogen-fixing symbioses with legumes. Most characterised

Mesorhizobium

spp. genomes are ~8 Mb in size and harbour extensive pangenomes including large integrative and conjugative elements (ICEs) carrying genes required for symbiosis (ICESyms). Here, we document and compare the conjugative mobilome of 41 complete

Mesorhizobium

genomes. We delineated 56 ICEs and 24 integrative and mobilizable elements (IMEs) collectively occupying 16 distinct integration sites, along with 24 plasmids. We also demonstrated horizontal transfer of the largest (853,775 bp) documented ICE, the tripartite ICEMspSymAA22. The conjugation systems of all identified ICEs and several plasmids were related to those of the paradigm ICESym ICEMlSymR7A, with each carrying conserved genes for conjugative pilus formation (trb), excision (rdfS), DNA transfer (rlxS) and regulation (fseA). ICESyms have likely evolved from a common ancestor, despite occupying a variety of distinct integration sites and specifying symbiosis with diverse legumes. We found extensive evidence for recombination between ICEs and particularly ICESyms, which all uniquely lack the conjugation entry-exclusion factor gene trbK. Frequent duplication, replacement and pseudogenization of genes for quorum-sensing-mediated activation and antiactivation of ICE transfer suggests ICE transfer regulation is constantly evolving. Pangenome-wide association analysis of the ICE identified genes potentially involved in symbiosis, rhizosphere colonisation and/or adaptation to distinct legume hosts. In summary, the

Mesorhizobium

genus has accumulated a large and dynamic pangenome that evolves through ongoing horizontal gene transfer of large conjugative elements related to ICEMlSymR7A.
“COVID-19 in twins: What can we learn from them?”
Authors: de Castro Mateus V , Silva Monize V R , Naslavsky Michel S , Santos Keity S , Magawa Jhosiene Y. , Neto Edecio Cunha , Passos-Bueno Maria Rita , Zatz Mayana
Published: October 2021

Investigations on the concordance in monozygotic (MZ) as compared to dizygotic (DZ) twins may reveal if there is a genetic component increasing the susceptibility or resistance against an infectious disease. Here, we compared the concordance rates of SARS-CoV-2 infection in MZ versus DZ young twins who shared the same bedrooms and were equally exposed to the virus. The concordance rate was higher in the MZ group supporting a complex multifactorial inheritance responsible for SARS-Cov-2 infection.
An outbreak report of the two autochthonous cases of airport malaria in Belgium in 2020
Authors: Van Bortel Wim , Van den Poel Bea , Hermans Greet , Driessche Marleen Vanden , Lerouge David , Deblauwe Isra , De Wolf Katrien , Schneider Anna , Van Hul Nick , Müller Ruth , Wilmaerts Leen , Gombeer Sophie , Smitz Nathalie , Kattenberg Johanna Helena , Monsieurs Pieter , Rosanas-Urgell Anna , Van Esbroeck Marjan , Bottieau Emmanuel , Maniewski-Kelner Ula , Rebolledo Javiera
Published: October 2021

We report an outbreak investigation of two fatal cases of autochthonous Plasmodium falciparum that occurred in Belgium in September 2020. Various hypotheses of potential source of infection were investigated. Based on the collected information, the most likely route of transmission was through an infectious exotic Anopheles mosquito that arrived via the international airport of Brussels or the Military airport Melsbroek and infected the cases who lived at five kilometres from the airports. Based on a genomic analysis of the parasites collected from the two cases, the most likely origin of the Plasmodium was Gabon or Cameroon. Further, the parasites collected from the two Belgian patients were identical-by-descent, which supports the assumption that the two infections originated from the bite of the same mosquito, during an interrupted feeding. Despite these cases, airport malaria remains a rare event. Yet, it has significant implications, particularly for the patient, as delayed or missed diagnosis of the cause of illness often results in high rates of complications and mortality. Therefore, to prevent such severe or fatal outcomes, a number of public health actions are suggested including increased awareness among health practitioners especially those working in the vicinity of airports and increased surveillance of exotic mosquito species at airports.