bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighbourhood stigma and place-based policies
Authors: Koster Hans R A , van Ommeren Jos
Published: July 2022

We analyse the effects of the Dutch Act on Extraordinary Measures for Urban Problems. This allows local governments to prohibit non-employed households from entering into public housing in targeted neighbourhoods to improve social mixing. We show that the Act is largely ineffective in changing the demographic composition of neighbourhoods. At the same time, due to prominent advertising of targeted deprived neighbourhoods, a stigma may have been created. We adopt a hedonic price approach and use a boundary-discontinuity (within 100 m of neighbourhood borders) to quantify the overall effect of the policy. We thus exploit spatio-temporal differences in house prices and find a sizeable price reduction of about 3–5%. The magnitude of this effect is confirmed for two other national place-based policy programmes, adding to the external validity of these findings. Our results suggest that neighbourhood stigma is important, which implies that individuals living in deprived neighbourhoods experience dis-utility from living in a place with a low status.
Neisseria gonorrhoeae-derived outer membrane vesicles package β-lactamases to promote antibiotic resistance
Authors: Dhital Subhash , Deo Pankaj , Bharathwaj Manasa , Horan Kristy , Nickson Joshua , Azad Mohammad , Stuart Isabella , Chow Seong H , Gunasinghe Sachith D , Bamert Rebecca , Li Jian , Lithgow Trevor , Howden Benjamin P , Naderer Thomas
Published: July 2022

Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhoea. The treatment of gonorrhoea is becoming increasingly challenging, as N. gonorrhoeae has developed resistance to antimicrobial agents routinely used in the clinic. Resistance to penicillin is wide-spread partly due to the acquisition of β-lactamase genes. How N. gonorrhoeae survives an initial exposure to β-lactams before acquiring resistance genes remains to be understood. Here, using a panel of clinical isolates of N. gonorrhoeae we show that the β-lactamase enzyme is packaged into outer membrane vesicles (OMVs) by strains expressing blaTEM-1B or blaTEM-106, which protects otherwise susceptible clinical isolates from the β-lactam drug amoxycillin. We characterized the phenotypes of these clinical isolates of N. gonorrhoeae and the time courses over which the cross-protection of the strains is effective. Imaging and biochemical assays suggest that OMVs promote the transfer of proteins and lipids between bacteria. Thus, N. gonorrhoeae strains secret antibiotic degrading enzymes via OMVs enabling survival of otherwise susceptible bacteria.
Evaluating Illumina-, Nanopore-, and PacBio-based genome assembly strategies with the bald notothen,Trematomus borchgrevinki
Authors: Rayamajhi Niraj , Cheng Chi-Hing Christina , Catchen Julian M
Published: July 2022

For any genome-based research, a robust genome assembly is required. De novo assembly strategies have evolved with changes in DNA sequencing technologies and have been through at least 3 phases: (1) short-read only, (2) short- and long-read hybrid, and (3) long-read only assemblies. Each of the phases has its own error model. We hypothesized that hidden short-read scaffolding errors and erroneous long-read contigs degrade the quality of short- and long-read hybrid assemblies. We assembled the genome of Trematomus borchgrevinki from data generated during each of the 3 phases and assessed the quality problems we encountered. We developed strategies such as k-mer-assembled region replacement, parameter optimization, and long-read sampling to address the error models. We demonstrated that a k-mer-based strategy improved short-read assemblies as measured by Benchmarking Universal Single-Copy Ortholog while mate-pair libraries introduced hidden scaffolding errors and perturbed Benchmarking Universal Single-Copy Ortholog scores. Furthermore, we found that although hybrid assemblies can generate higher contiguity they tend to suffer from lower quality. In addition, we found long-read-only assemblies can be optimized for contiguity by subsampling length-restricted raw reads. Our results indicate that long-read contig assembly is the current best choice and that assemblies from phase I and phase II were of lower quality.
Interpretation of time reversal focal spots based on point-source homogenization
Authors: Renat Zoé , Cupillard Paul , Capdeville Yann
Published: July 2022

The time reversal method is based on the backpropagation of seismic waveforms recorded at a set of receivers. When this set forms a closed surface and the elastic properties of the medium are correct, the seismic energy focuses at the source location, creating a focal spot. Such a spot is smooth in space, whereas the original wavefield usually shows a displacement discontinuity at the source. The goal of this paper is to discuss the link between the focal spot and the original source using the concept of homogenized point source. We show that the backpropagated wavefield is equivalent to the sum of two low-wavenumber fields resulting from the homogenization of the original point source. In other words, the homogenized point source is the equivalent force for producing the focal spot. In addition to the demonstration in the general 3-D heterogeneous case, we present some numerical examples in 2-D.
Complexity and evidence in health sector decision-making: lessons from tuberculosis infection prevention in South Africa
Authors: Perera Shehani , Parkhurst Justin , Diaconu Karin , Bozzani Fiammetta , Vassall Anna , Grant Alison , Kielmann Karina
Published: July 2022

To better understand and plan health systems featuring multiple levels and complex causal elements, there have been increasing attempts to incorporate tools arising from complexity science to inform decisions. The utilization of new planning approaches can have important implications for the types of evidence that inform health policymaking and the mechanisms through which they do so. This paper presents an empirical analysis of the application of one such tool—system dynamics modelling (SDM)—within a tuberculosis control programme in South Africa in order to explore how SDM was utilized, and to reflect on the implications for evidence-informed health policymaking. We observed group model building workshops that served to develop the SDM process and undertook 19 qualitative interviews with policymakers and practitioners who partook in these workshops. We analysed the relationship between the SDM process and the use of evidence for policymaking through four conceptual perspectives: (1) a rationalist knowledge-translation view that considers how previously-generated research can be taken up into policy; (2) a programmatic approach that considers existing goals and tasks of decision-makers, and how evidence might address them; (3) a social constructivist lens exploring how the process of using an evidentiary planning tool like SDM can shape the understanding of problems and their solutions; and (4) a normative perspective that recognizes that stakeholders may have different priorities, and thus considers which groups are included and represented in the process. Each perspective can provide useful insights into the SDM process and the political nature of evidence use. In particular, SDM can provide technical information to solve problems, potentially leave out other concerns and influence how problems are conceptualized by formalizing the boundaries of the policy problem and delineating particular solution sets. Undertaking the process further involves choices on stakeholder inclusion affecting whose interests may be served as evidence to inform decisions.
Opposing effects of genetic variation in MTCH2 for obesity versus heart failure
Authors: Fischer Julie A , Monroe Tanner O , Pesce Lorenzo L , Sawicki Konrad T , Quattrocelli Mattia , Bauer Rosemary , Kearns Samuel D , Wolf Matthew J , Puckelwartz Megan J , McNally Elizabeth M
Published: July 2022

Genetic variation in genes regulating metabolism may be advantageous in some settings but not others. The non-failing adult heart relies heavily on fatty acids as a fuel substrate and source of ATP. In contrast, the failing heart favors glucose as a fuel source. A bootstrap analysis for genes with deviant allele frequencies in cardiomyopathy cases versus controls identified the MTCH2 gene as having unusual variation. MTCH2 encodes an outer mitochondrial membrane protein, and prior genome-wide studies associated MTCH2 variants with body mass index, consistent with its role in metabolism. We identified the referent allele of rs1064608 (p.Pro290) as being overrepresented in cardiomyopathy cases compared to controls, and linkage disequilibrium analysis associated this variant with the MTCH2 cis eQTL rs10838738 and lower MTCH2 expression. To evaluate MTCH2, we knocked down Mtch in Drosophila heart tubes which produced a dilated and poorly functioning heart tube, reduced adiposity and shortened life span. Cardiac Mtch mutants generated more lactate at baseline, and they displayed impaired oxygen consumption in the presence of glucose but not palmitate. Treatment of cardiac Mtch mutants with dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, reduced lactate and rescued lifespan. Deletion of MTCH2 in human cells similarly impaired oxygen consumption in the presence of glucose but not fatty acids. These data support a model in which MTCH2 reduction may be favorable when fatty acids are the major fuel source, favoring lean body mass. However, in settings like heart failure, where the heart shifts toward using more glucose, reduction of MTCH2 is maladaptive.
Identification of new RAD51D-regulating microRNAs that also emerge as potent inhibitors of the Fanconi anemia/homologous recombination pathways
Authors: Hater Nina , Iwaniuk Katharina M , Leifeld Carina , Grüten Pia , Wiek Constanze , Raba Katharina , Zhang Fan , Fischer Johannes C , Andreassen Paul R , Hanenberg Helmut , Trompeter Hans-Ingo
Published: July 2022

The Fanconi anemia (FA) and homologous recombination (HR) pathways, which partially overlap and include RAD51 and its paralogs, are key for the repair of different types of DNA damage, such as DNA interstrand crosslinks. First, to broadly assess the impact of microRNA-mediated regulation, we examined microRNA expression profiles in five isogenic fibroblast cell pairs, either deficient in DNA repair due to germline mutations in FANCA, FANCB, FANCC, FANCI or BRIP1/FANCJ or proficient due to correction with retroviral vectors. In each pair, we observed lower abundance of specific microRNAs in the FA-deficient cells. From the list of microRNAs, we experimentally confirmed the effects of miR-141-3p and miR-369-3p targeting RAD51B and miR-15a-5p, miR-494-3p as well as miR-544a targeting RAD51D. However, by western blotting, only RAD51D protein was reduced by a mixture of its regulating microRNAs. Gene ontology analyses and identification of additional FA/HR factors as targets of miR-15a-5p, miR-494-3p and miR-544a strongly suggested the widespread influence of these microRNAs on HR. Interestingly, only miR-494-3p directly reduced RAD51 foci formation, while a mixture of miR-15a-5p, miR-494-3p and miR-544a strongly reduced HR activity in green fluorescent protein (GFP) repair assays. In summary, by successfully employing this novel loss- and gain-of-function strategy, we have identified new microRNAs strongly inhibiting HR in mammalian cells. Understanding and modulating such miRNA regulation of DNA repair genes/pathways might help to overcome the reduced repair capacity of FA patients with biallelic hypomorphic mutations or help to engineer synthetic lethality strategies for patients with mutations in cancer-associated FA/HR genes.
Early Initiation of Antitumor Necrosis Factor Therapy Reduces Postoperative Recurrence of Crohn’s Disease Following Ileocecal Resection
Authors: Axelrad Jordan E , Li Terry , Bachour Salam P , Nakamura Takahiro I , Shah Ravi , Sachs Michael C , Chang Shannon , Hudesman David P , Holubar Stefan D , Lightner Amy L , Barnes Edward L , Cohen Benjamin L , Rieder Florian , Esen Eren , Remzi Feza , Regueiro Miguel , Click Benjamin
Published: July 2022

Background

Postoperative recurrence (POR) of Crohn’s disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR).

Methods

We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (≥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab).

Results

We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis.

Conclusion

Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited.
Prevalence of Clostridioides difficile Infection After Ileal Pouch-anal Anastomosis in Patients With Chronic Antibiotic-dependent Pouchitis and Crohn’s-like Disease of the Pouch
Authors: Shore Brandon M , Weaver Kimberly N , Allegretti Jessica R , Herfarth Hans H , Barnes Edward L
Published: July 2022

Background

Recurrent or chronic antibiotic therapy is a therapeutic hallmark of chronic antibiotic-dependent pouchitis (CADP) or Crohn’s-like disease of the pouch. Antibiotics alter the gut microbiome, which may increase the risk of Clostridioides difficile infection (CDI). The aim of this study was to determine the prevalence of CDI in patients with CADP and Crohn’s-like disease of the pouch.

Methods

We conducted a retrospective cohort study of patients with CADP or Crohn’s-like disease of the pouch at a tertiary academic medical center. The primary outcome was prevalence of CDI. Secondary outcomes included antibiotic therapy at the time of CDI diagnosis, treatment regimens for CDI, and subsequent outcomes.

Results

Overall, 18 of 198 (9.1%) included patients developed CDI. Treatment with antibiotics at the time of CDI diagnosis occurred in 7 of 18 (39%) patients. Preoperative history of CDI was significantly associated with increased risk of developing CDI following ileal pouch anal anastomosis (IPAA) compared with those with no prior history of CDI (12 of 18 [67%] vs 11 of 180 [6%]; P < .001). In 16 of 18 (89%) patients, CDI treatment was initiated with predominantly oral vancomycin (72%) or metronidazole (17%).

Conclusion

Although chronic inflammatory conditions of the pouch arise postoperatively, the prevalence of CDI in this population appears to be similar compared with the general population of patients with inflammatory bowel disease prior to and post IPAA. Preoperative CDI appears to be the greatest risk for postoperative CDI and may require extra vigilance in the assessment of CDI after IPAA.
Perioperative electroencephalography in cardiac surgery with hypothermic circulatory arrest: a narrative review
Authors: McDevitt William M , Gul Tanwir , Jones Timothy J , Scholefield Barnaby R , Seri Stefano , Drury Nigel E
Published: July 2022

OBJECTIVES

Cardiac surgery with hypothermic circulatory arrest (HCA) is associated with neurological morbidity of variable severity and electroencephalography (EEG) is a sensitive proxy measure of brain injury. We conducted a narrative review of the literature to evaluate the role of perioperative EEG monitoring in cardiac surgery involving HCA.

METHODS

Medline, Embase, Central and LILACS databases were searched to identify studies utilizing perioperative EEG during surgery with HCA in all age groups, published since 1985 in any language. We aimed to compare EEG use with no use but due to the lack of comparative studies, we performed a narrative review of its utility. Two or more reviewers independently screened studies for eligibility and extracted data.

RESULTS

Fourty single-centre studies with a total of 3287 patients undergoing surgery were identified. Most were observational cohort studies (34, 85%) with only 1 directly comparing EEG use with no use. EEG continuity (18, 45%), seizures (15, 38%) and electrocerebral inactivity prior to circulatory arrest (15, 38%) were used to detect, monitor, prevent and prognose neurological injury. Neurological dysfunction was reported in almost all studies and occurred in 0–21% of patients. However, the heterogeneity of reported clinical and EEG outcome measures prevented meta-analysis.

CONCLUSIONS

EEG is used to detect cortical ischaemia and seizures and predict neurological abnormalities and may guide intraoperative cerebral protection. However, there is a lack of comparative data demonstrating the benefit of perioperative EEG monitoring. Use of a standardized methodology for performing EEG and reporting outcome metrics would facilitate the conduct of high-quality clinical trials.
Approximation of fractional harmonic maps
Authors: Antil Harbir , Bartels Sören , Schikorra Armin
Published: July 2022

This paper addresses the approximation of fractional harmonic maps. Besides a unit-length constraint, one has to tackle the difficulty of nonlocality. We establish weak compactness results for critical points of the fractional Dirichlet energy on unit-length vector fields. We devise and analyze numerical methods for the approximation of various partial differential equations related to fractional harmonic maps. The compactness results imply the convergence of numerical approximations. Numerical examples on spin chain dynamics and point defects are presented to demonstrate the effectiveness of the proposed methods.
Understanding the suitability of established antibiotics for oral inhalation from a pharmacokinetic perspective: an integrated model-based investigation based on rifampicin, ciprofloxacin and tigecycline in vivo data
Authors: Himstedt Anneke , Braun Clemens , Wicha Sebastian Georg , Borghardt Jens Markus
Published: July 2022

Background

Treating pulmonary infections by administering drugs via oral inhalation represents an attractive alternative to usual routes of administration. However, the local concentrations after inhalation are typically not known and the presumed benefits are derived from experiences with drugs specifically optimized for inhaled administration.

Objectives

A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was developed to elucidate the pulmonary PK for ciprofloxacin, rifampicin and tigecycline and link it to bacterial PK/PD models. An exemplary sensitivity analysis was performed to potentially guide drug optimization regarding local efficacy for inhaled antibiotics.

Methods

Detailed pulmonary tissue, endothelial lining fluid and systemic in vivo drug concentration–time profiles were simultaneously measured for all drugs in rats after intravenous infusion. Using this data, a PBPK/PD model was developed, translated to humans and adapted for inhalation. Simulations were performed comparing potential benefits of oral inhalation for treating bronchial infections, covering intracellular pathogens and bacteria residing in the bronchial epithelial lining fluid.

Results

The PBPK/PD model was able to describe pulmonary PK in rats. Often applied optimization parameters for orally inhaled drugs (e.g. high systemic clearance and low oral bioavailability) showed little influence on efficacy and instead mainly increased pulmonary selectivity. Instead, low permeability, a high epithelial efflux ratio and a pronounced post-antibiotic effect represented the most impactful parameters to suggest a benefit of inhalation over systemic administration for locally acting antibiotics.

Conclusions

The present work might help to develop antibiotics for oral inhalation providing high pulmonary concentrations and fast onset of exposure coupled with lower systemic drug concentrations.
Activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam and cefepime/zidebactam against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa
Authors: Lasarte-Monterrubio Cristina , Fraile-Ribot Pablo Arturo , Vázquez-Ucha Juan Carlos , Cabot Gabriel , Guijarro-Sánchez Paula , Alonso-García Isaac , Rumbo-Feal Soraya , Galán-Sánchez Fátima , Beceiro Alejandro , Arca-Suárez Jorge , Oliver Antonio , Bou Germán
Published: July 2022

Objectives

To evaluate the activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam and cefepime/zidebactam against a clinical and laboratory collection of ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa β-lactamase mutants.

Methods

The activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam, cefepime/zidebactam and comparators was evaluated against a collection of 30 molecularly characterized ceftolozane/tazobactam- and/or ceftazidime/avibactam-resistant P. aeruginosa isolates from patients previously treated with cephalosporins. To evaluate how the different β-lactamases in the clinical isolates affected the resistance to these agents, a copy of each blaPDC, blaOXA-2 and blaOXA-10 ancestral and mutant allele from the clinical isolates was cloned in pUCp24 and expressed in dual blaPDC-oprD (for blaPDC-like genes) or single oprD (for blaOXA-2-like and blaOXA-10-like genes) PAO1 knockout mutants. MICs were determined using reference methodologies.

Results

For all isolates, MICs were higher than 4 and/or 8 mg/L for ceftolozane/tazobactam and ceftazidime/avibactam, respectively. Cefiderocol was the most active agent, showing activity against all isolates, except one clinical isolate that carried an R504C substitution in PBP3 (MIC = 16 mg/L). Imipenem/relebactam was highly active against all isolates, except two clinical isolates that carried the VIM-20 carbapenemase. Cefepime/zidebactam and cefepime/taniborbactam displayed activity against most of the isolates, but resistance was observed in some strains with PBP3 amino acid substitutions or that overexpressed mexAB-oprM or mexXY efflux pumps. Evaluation of transformants revealed that OXA-2 and OXA-10 extended-spectrum variants cause a 2-fold increase in the MIC of cefiderocol relative to parental enzymes.

Conclusions

Cefiderocol, imipenem/relebactam, cefepime/taniborbactam and cefepime/zidebactam show promising and complementary in vitro activity against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant P. aeruginosa. These agents may represent potential therapeutic options for ceftolozane/tazobactam- and ceftazidime/avibactam-resistant P. aeruginosa infections.
Plasmodium falciparum merozoite invasion ligands, linked antimalarial resistance loci and ex vivo responses to antimalarials in The Gambia
Authors: Mbye Haddijatou , Mane Karim , Diop Mouhamadou Fadel , Demba Martha Anita , Bojang Fatoumata , Mohammed Nuredin Ibrahim , Jeffries David , Quashie Neils Ben , D’Alessandro Umberto , Amambua-Ngwa Alfred
Published: July 2022

Background

Artemether/lumefantrine is the most commonly used artemisinin-based combination treatment (ACT) for malaria in sub-Saharan Africa. Drug resistance to ACT components is a major threat to malaria elimination efforts. Therefore, rigorous monitoring of drug efficacy is required for adequate management of malaria and to sustain the effectiveness of ACTs.

Objectives

This study identified and described genomic loci that correlate with differences in ex vivo responses of natural Plasmodium falciparum isolates from The Gambia to antimalarial drugs.

Methods

Natural P. falciparum isolates from The Gambia were assayed for IC50 responses to four antimalarial drugs (artemether, dihydroartemisinin, amodiaquine and lumefantrine). Genome-wide SNPs from 56 of these P. falciparum isolates were applied to mixed-model regression and network analyses to determine linked loci correlating with drug responses. Genomic regions of shared haplotypes and positive selection within and between Gambian and Cambodian P. falciparum isolates were mapped by identity-by-descent (IBD) analysis of 209 genomes.

Results

SNPs in 71 genes, mostly involved in stress and drug resistance mechanisms correlated with drug responses. Additionally, erythrocyte invasion and permeability loci, including merozoite surface proteins (Pfdblmsp, Pfsurfin), and high-molecular-weight rhoptry protein 2 (Pfrhops2) were correlated with responses to multiple drugs. Haplotypes of pfdblmsp2 and known drug resistance loci (pfaat1, pfcrt and pfdhfr) from The Gambia showed high IBD with those from Cambodia, indicating co-ancestry, with significant linkage disequilibrium between their alleles.

Conclusions

Multiple linked genic loci correlating with drug response phenotypes suggest a genomic backbone may be under selection by antimalarials. This calls for further analysis of molecular pathways to drug resistance in African P. falciparum.
Unmet needs and practical solutions in the management of invasive mould infections in Asia
Authors: Chen Yee Chun , Chayakulkeeree Methee , Chakrabarti Arunaloke , Gan Gin Gin , Kwong Yok Lam , Liu Wei-Lun , Tan Ban Hock , Todi Subhash
Published: July 2022

Management of invasive mould infections (IMIs) is challenging in Asia, as awareness among medical practitioners can be low and resources are limited. Timely diagnosis and appropriate treatment of IMIs can mitigate the impact on morbidity and mortality, but diagnostic methods, as well as access to preferred antifungal medications, may vary throughout the region. Knowledge of local epidemiology and accurate diagnosis and identification of causal pathogens would facilitate optimal treatment but data in Asia are lacking. To address these unmet needs in the management of IMIs, this paper is a call for urgent action in the following areas: improving awareness of the threat of IMIs; providing education to frontline clinicians across a broad range of specialties on ‘red flags’ for suspicion of IMIs; prioritizing cost-effective rapid diagnostic testing; improving access to preferred antifungal medications; and closing the gaps in local epidemiological data on IMIs to inform local treatment guidelines.
Electronic case reporting (eCR) of COVID-19 to public health: implementation perspectives from the Minnesota Department of Health
Authors: Rajamani Sripriya , Kayser Ann , Ruprecht Ali , Cassman Jacqueline , Polzer Megan , Homan Teri , Reid Ann , Hanson Melinda , Emerson Emily , Dahlberg Schmit Aasa , Solarz Sarah
Published: July 2022

Electronic case reporting (eCR) is the automated generation and transmission of case reports from electronic health records to public health for review and action. These reports (electronic initial case reports: eICRs) adhere to recommended exchange and terminology standards. eCR is a partnership of the Centers for Disease Control and Prevention (CDC), Association of Public Health Laboratories (APHL) and Council of State and Territorial Epidemiologists (CSTE). The Minnesota Department of Health (MDH) received eICRs for COVID-19 from April 2020 (3 sites, manual process), automated eCR implementation in August 2020 (7 sites), and on-boarded ∼1780 clinical units in 460 sites across 6 integrated healthcare systems (through March 2022). Approximately 20 000 eICRs/month were reported to MDH during high-volume timeframes. With increasing provider/health system implementation, the proportion of COVID-19 cases with an eICR increased to 30% (March 2022). Evaluation of data quality for select demographic variables (gender, race, ethnicity, email, phone, language) across the 6 reporting health systems revealed a high proportion of completeness (>80%) for half of variables and less complete data for rest (ethnicity, email, language) along with low ethnicity data (<50%) for one health system. Presently eCR implementation at MDH includes only one EHR vendor. Next steps will focus on onboarding other EHRs, additional eICR data extraction/utilization, detailed analysis, outreach to address data quality issues, and expanding to other reportable conditions.
Chemometric Quality Assessment of Doxylamine Succinate With Its Degradation Product: Implementation of Two Predictive Models on UV-Spectrophotometric Data of Anti-Emetic Binary Mixture
Authors: Abd El-Hadi Heidi R , Eissa Maya S , Zaazaa Hala E , Eltanany Basma M
Published: July 2022

Background

The combination of pyridoxine hydrochloride (PYR) and doxylamine succinate (DOX) as an antiemetic binary mixture is used to treat nausea and vomiting during pregnancy.

Objective

Two validated, accurate, and selective chemometric models were developed to assay binary mixture in the presence of DOX oxidative degradation product (DOX DEG) that could be characterized using LC-MS.

Methods

Partial least squares (PLS) regression and principal component regression (PCR) were selected for the determination of our binary mixture in presence of degradation. To exhibit a training set of 25 mixtures that had various percentages of tested substances in five level 3 variables, an experimental design was chosen. A set of 18 synthetic mixtures in the concentration range 10.0–50.0 μg/mL, 12.00–20.0 μg/mL, and 6.0–30.0 μg/mL for PYR, DOX, and DOX DEG, respectively, were used in the construction of the calibration models. Then set of seven synthetic mixtures with different concentrations were used in the construction of the validation models.

Results

In validation samples with low root mean square error of prediction (RMSEP), the suggested models successfully predicted the concentrations of our drugs. The models developed were evaluated by RMSEP calculation, and the values obtained were 0.341, 0.196, and 0.388 for PYR, DOX, and DOX DEG, respectively, using PLS. While using PCR, RMSEP calculation and the values obtained were 0.400, 0.256, and 0.375 for PYR, DOX, and DOX DEG, respectively. The developed models were validated according to ICH strategies.

Conclusions

The corresponding methods are suitable to determine PYR and DOX in pure form, pharmaceutical dosage form, and in the presence of DOX DEG product.

Highlights

The study of drug breakdown pathways is very important nowadays, so even in the presence of degradation and extreme spectral overlapping, the suggested PLS and PCR spectrophotometric approaches were able to identify PYR and DOX.
Biomechanical effects of bone quality and design features in dental implants in long-term bone stability
Authors: Park Jieun , Park Soyeon , Kang Inyeong , Noh Gunwoo
Published: July 2022

This study analyzed the effects of implant design factors (diameter, length, and connection type) and bone quality on the long-term success of implantation via finite element (FE) analysis, considering the bone remodeling process. A total of 36 cases of the three-dimensional FE model, with an implant complex located in the mandibular bone section of the molar region, were considered. An FE analysis considering dental bone remodeling was implemented in the Abaqus UMAT subroutine. A preload of 32 N∙cm and an average biting force of 50 N were applied during the bone remodeling process as the loading conditions. After the bone remodeling process, a maximum biting force of 200 N was applied in the oblique direction. The stability of the peri-implant bone was analyzed by measuring the apparent bone density over time and the principal strain in the cancellous bone. The stability of the peri-implant bone differs depending on the host bone conditions and implant design features. The initial bone condition greatly influenced the final density and maximum principal strain distribution in the cancellous bone surrounding the implant. The need for a stability evaluation considering the bone remodeling process has increased under the conditions of placing short-length and narrow-diameter implants in poor-quality bones.
Computed tomography vertebral segmentation from multi-vendor scanner data
Authors: Kim Chaewoo , Bekar Oguzcan , Seo Hyunseok , Park Sang-Min , Lee Deukhee
Published: July 2022

Automatic medical image segmentation is a crucial procedure for computer-assisted surgery. Especially, three-dimensional reconstruction of medical images of the surgical targets can be accurate in fine anatomical structures with optimal image segmentation, thus leading to successful surgical results. However, the performance of the automatic segmentation algorithm highly depends on the consistent properties of medical images. To address this issue, we propose a model for standardizing computed tomography (CT) images. Hence, our CT image-to-image translation network enables diverse CT images (non-standard images) to be translated to images with identical features (standard images) for the more precise performance of U-Net segmentation. Specifically, we combine an image-to-image translation network with a generative adversarial network, consisting of a residual block-based generative network and the discriminative network. Also, we utilize the feature extracting layers of VGG-16 to extract the style of the standard image and the content of the non-standard image. Moreover, for precise diagnosis and surgery, the conservation of anatomical information of the non-standard image is also essential during the synthesis of medical images. Therefore, for performance evaluation, largely three evaluation methods are employed: (i) visualization of the geometrical matching between the non-standard (content) and synthesized images to verify the maintenance of the anatomical structures; (ii) measuring numerical results using image similarity evaluation metrics; and (iii) assessing the performance of U-Net segmentation with our synthesized images. Specifically, we investigate that our model network can transfer the texture from standard CT images to diverse CT images (non-standard) scanned by different scanners and scan protocols. Also, we verify that the synthesized images can retain the global pose and fine structures of the non-standard images. We also compare the predicted segmentation result of the non-standard image and the synthesized image generated from its non-standard image via our proposed network. In addition, the performance of our proposed model is compared with the windowing process, where the window parameter of the standard image is applied to the non-standard image to ensure that our model outperforms the windowing process.
Optimal design of classic RCD absorption circuit in transient electromagnetic transmitter
Authors: Zhou Sheng , Zhao Xiang , Xi Zhenzhu , Qi Qingxin , Wang He , Long Xia
Published: July 2022

The classic RCD absorption circuit has been applied to shorten the turn-off time of transmitters. The current way to determine the resistor and capacitor values of the classic RCD circuit is inefficient. In this paper, an intelligent optimization method to design the classic RCD absorption circuit is proposed. First, based on Kirchhoff's law, the working principles of the RCD absorption circuit at three phases are mathematically analyzed. The formulations of current and voltage at each phase are derived. Next, the shortest turn-off time and its corresponding capacitance and resistance are determined using modeling. Finally, tests are carried out with the transmitting board and antenna to verify the simulation results. Compared with existing method, this new method is easier to operate, and it is more efficient at getting a accurate minimum turn-off time for a given transmitter loop.
An efficient symplectic stereo-modeling method for seismic inversion by using deep learning technique
Authors: Zhou Yanjie , Lu Fan , Ma Xiao , Huang Xueyuan , Wang Chenguang , He Xijun
Published: July 2022

This paper proposes an efficient symplectic stereo-modeling (SSTEM) method for full waveform inversion (FWI) by using a deep learning technique. To solve the 2D acoustic equation, the SSTEM method uses a third-order optimal symplectic partitioned Runge–Kutta approach as a time-stepping method. An eighth-order stereo-modeling operator is used for spatial discretization. The SSTEM method is then expressed with a recurrent neural network (RNN). This is realized mainly because the time advancing format of the SSTEM method is similar to that of RNN, and they both use the information from the previous time step to obtain information from the current time step. With SSTEM as the forward modeling method, FWI is implemented using Tensorflow. The well-known adaptive moment estimation (Adam) optimizer and Nesterov adaptive moment estimation (Nadam) optimizer with mini-batch are used. The applicability of the developed code is also verified on GPUs. The numerical results show that the SSTEM method is more efficient and produces less numerical dispersion than the conventional finite-difference (FD) method when the same sampling rate in a wavelength is used. We compare several loss functions. The mean square (MSE) error and absolute (ABS) error loss functions are first tested. Another loss function that adds a physical differential operator to the original loss function is then considered. The FWI results show that this loss function has some improvements. Finally, we implement FWI on the complex Marmousi and SEG/EAGE models, and the inversion results demonstrate that the proposed method is suitable for seismic imaging in complex media.
Suppressing the very low-frequency noise by B-spline gating of transient electromagnetic data
Authors: Peng Cong , Zhu Kaiguang , Fan Tianjiao , Yang Yang
Published: July 2022

Very low-frequency (VLF) communication signals of 15–25 kHz contaminate the transient electromagnetic (TEM) data. The notch filter or Butterworth filter is commonly used to suppress VLF noise in addition to synchronous detection of TEM data such as gating and stacking, while also introducing the TEM signal distortion around the VLF band. We propose a B-spline gating, which suppresses the VLF noise while integrating TEM data in the gate interval without any extra filter. B-spline gating is designed to ensure that the zeros of its amplitude frequency response (AFR) are located around VLF frequencies by optimizing the knot vector of the B-spline. It is available for various VLF frequencies. We apply B-spline gating to synthetic TEM data compared with rectangular gating and full-tapered gating, the AFRs of B-spline and full-tapered gating are 25 dB lower at high frequencies than rectangular gating, and the amplitude of B-spline is more reduced at VLF frequency than full-tapered gating; the standard error of the B-spline gates is reduced by >15% compared to the full-tapered gates. The field example from a TEM survey in the Inner Mongolia Autonomous Region of China shows that the amplitude of B-spline gating frequency response in late gates is reduced by about 20 dB at 24.1 kHz VLF than that of full-tapered gating, and the standard error is lower. It is concluded that B-spline gating can suppress VLF noise while following the normal decay of TEM signal without distortion.
An ATEM 1D inversion based on K-Means clustering and MLP deep learning
Authors: Shi Mingzhi , Cao Hui
Published: July 2022

Traditional geophysical inversion methods rely on an assumption of prior knowledge, starting from the establishment of the initial model and ending with the model being modified many times. This iterative process makes the forward modelling results move increasingly closer to the observed data. However, each inversion step requires multiple forward calculations, which consumes considerable time and computing resources. This is the greatest obstacle to real-time inversion at present. Airborne transient electromagnetic (ATEM) response data are collected in a time-channel manner. The different stratigraphic structures reveal different time-varying electromagnetic response laws. In this paper, deep learning technology is used to advance the ‘model correction-forward iteration’ step in the geophysical inversion process to the data preprocessing stage, to better adapt to the specialty of ATEM, improve the efficiency of the inversion and shorten the inversion time. In this method, a sample set composed of a ‘stratigraphic texture model—ATEM response’ is established, the K-Means clustering technique of unsupervised learning is used to complete the sample tag attachment, and the multilayer perceptron (MLP) deep learning network with supervised learning is used to complete the multiclassification tasks. Then, the sample sets are input into the deep learning network for training to build the inversion from the input response data to the output of the stratigraphic model. Finally, the inversion flow is verified with test set samples. The prediction results are consistent with the simulated data, and the inversion, from the test data to the prediction model, is implemented efficiently.
‘His utter unfitness for a commercial collector’
Authors: Alcorn Keith
Published: July 2022

Non-European or ‘exotic’ plants became prestigious collectable items in the early nineteenth century. Although unpaid collectors contributed greatly to the discovery of new plants, systematic sponsored collecting became increasingly important after 1800 in Britain. While sharing features of natural history collecting, the organization and sponsorship of exotic plant collecting in the first half of the nineteenth century in Britain exhibits several distinctive features, notably the involvement of commercial sponsors and cooperation between commercial and scientific bodies. Using the Directors’ Correspondence of the Royal Botanic Gardens, Kew, this article describes how individuals, consortia of sponsors and subscription systems assembled finance for plant collecting. The article demonstrates the extent to which plant introductions depended on a structured trade in plants, in which commercial nurseries played a central role. Plant collecting must be understood as an episode not only in the history of garden design, but also in the history of collections.
Estimation of projection parameter distribution and initial model generation in single-particle analysis
Authors: Mamizu Nobuya , Yasunaga Takuo
Published: July 2022

This study focused on the problem of projection parameter search in 3D reconstruction using single-particle analysis. We treated the sampling distribution for the parameter search as a prior distribution and designed a probabilistic model for efficient parameter estimation. Using our method, we showed that it is possible to perform 3D reconstruction from synthetic and actual electron microscope images using an initial model and to generate the initial model itself. We also examined whether the optimization function used in the stochastic gradient descent method can be applied with loose constraints to improve the convergence of initial model generation and confirmed the effect. In order to investigate the advantage of generating a smooth sampling distribution from the stochastic model, we compared the distribution of estimated projection directions with the conventional method of performing a global search using spherical gridding. As a result, our method, which is simple in both mathematical model and implementation, showed no algorithmic artifacts.
Tau Pathology in Chronic Traumatic Encephalopathy is Primarily Neuronal
Authors: Butler Morgane L M D , Dixon Erin , Stein Thor D , Alvarez Victor E , Huber Bertrand , Buckland Michael E , McKee Ann C , Cherry Jonathan D
Published: July 2022

Millions of individuals are exposed to repetitive head impacts (RHI) each year through contact sports, military blast, and interpersonal violence. RHI is the major risk factor for developing chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. Recent consensus criteria defined the pathognomonic lesion in CTE as perivascular, hyperphosphorylated tau (p-tau) in neuronal aggregates. Astroglial p-tau is an inconsistent supporting feature and not in itself diagnostic of CTE. This study quantitated the spatial and cellular distribution of p-tau pathology in postmortem dorsolateral frontal cortex of 150 individuals with CTE, from ages 21 to 80 years old, without comorbid pathology. p-Tau-immunoreactive cells were quantitated in the gray matter sulcus, crest, subpial region, and within pathognomonic CTE lesions. Significantly more neuronal p-tau than astrocytic p-tau was found across all cortical regions (p < 0.0001). Sulcal astrocytic p-tau was primarily (75%, p < 0.0001) localized to subpial regions as thorn-shaped astrocytes, a form of age-related tau astrogliopathy. Neuronal p-tau was significantly associated with age, years of RHI exposure, and CTE severity; astrocytic p-tau pathology was only significantly associated with age. These findings strongly support neuronal degeneration as a driving feature of CTE and will help inform future research and the development of fluid biomarkers for the detection of neuronal degeneration in CTE.
Safety and Acceptance of COVID-19 Vaccination After Multisystem Inflammatory Syndrome in Children (MIS-C) in Spain
Authors: Epalza Cristina , Prieto-Tato Luis , Pino Rosa , Escartín-Paredes Paula , Leoz Inés , Grasa Carlos , Vivanco-Allende Ana , Rivière Jacques G , Carrasco-Colom Jaume , Villate Olatz , Fumadó Victoria , Hermoso-Ibañez Concepción , Herrero Blanca , Aguilera-Alonso David , Tagarro Alfredo , Moraleda Cinta ,   EPICO-AEP Working Group
Published: July 2022

In this cohort of 42 adolescents with a previous multisystem inflammatory syndrome (MIS-C) diagnosis, 32 (76.2%) were vaccinated with COVID-19 vaccines, with a low incidence of relevant adverse events. More importantly, no new MIS-C or myocarditis occurred after a median of 10 weeks (range 5.3-19.7) post-vaccination.
Enhanced abundance and activity of the chloroplast ATP synthase in rice through the overexpression of the AtpD subunit
Authors: Ermakova Maria , Heyno Eiri , Woodford Russell , Massey Baxter , Birke Hannah , von Caemmerer Susanne
Published: July 2022

ATP, produced by the light reactions of photosynthesis, acts as the universal cellular energy cofactor fuelling all life processes. Chloroplast ATP synthase produces ATP using the proton motive force created by solar energy-driven thylakoid electron transport reactions. Here we investigate how increasing abundance of ATP synthase affects leaf photosynthesis and growth of rice, Oryza sativa variety Kitaake. We show that overexpression of AtpD, the nuclear-encoded subunit of the chloroplast ATP synthase, stimulates both abundance of the complex, confirmed by immunodetection of thylakoid complexes separated by Blue Native-PAGE, and ATP synthase activity, detected as higher proton conductivity of the thylakoid membrane. Plants with increased AtpD content had higher CO2 assimilation rates when a stepwise increase in CO2 partial pressure was imposed on leaves at high irradiance. Fitting of the CO2 response curves of assimilation revealed that plants overexpressing AtpD had a higher electron transport rate (J) at high CO2, despite having wild-type-like abundance of the cytochrome b6f complex. A higher maximum carboxylation rate (Vcmax) and lower cyclic electron flow detected in transgenic plants both pointed to an increased ATP production compared with wild-type plants. Our results present evidence that the activity of ATP synthase modulates the rate of electron transport at high CO2 and high irradiance.