bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitoxin Use in the Prevention and Treatment of Anthrax Disease: A Systematic Review
Authors: Hesse Elisabeth M , Godfred-Cato Shana , Bower William A
Published: October 2022

Background

Bacillus anthracis is a high-priority threat agent because of its widespread availability, easy dissemination, and ability to cause substantial morbidity and mortality. Although timely and appropriate antimicrobial therapy can reduce morbidity and mortality, the role of adjunctive therapies continues to be explored.

Methods

We searched 11 databases for articles that report use of anthrax antitoxins in treatment or prevention of systemic anthrax disease published through July 2019. We identified other data sources through reference search and communication with experts. We included English-language studies on antitoxin products with approval by the US Food and Drug Administration (FDA) for anthrax in humans, nonhuman primates, and rabbits. Two researchers independently reviewed studies for inclusion and abstracted relevant data.

Results

We abstracted data from 12 publications and 2 case reports. All 3 FDA-approved anthrax antitoxins demonstrated significant improvement in survival as monotherapy over placebo in rabbits and nonhuman primates. No study found significant improvement in survival with combination antitoxin and antimicrobial therapy compared to antimicrobial monotherapy. Case reports and case series described 25 patients with systemic anthrax disease treated with antitoxins; 17 survived. Animal studies that used antitoxin monotherapy as postexposure prophylaxis (PEP) demonstrated significant improvement in survival over placebo, with greatest improvements coming with early administration.

Conclusions

Limited human and animal evidence indicates that adjunctive antitoxin treatment may improve survival from systemic anthrax infection. Antitoxins may also provide an alternative therapy to antimicrobials for treatment or PEP during an intentional anthrax incident that could involve a multidrug-resistant B. anthracis strain.
Safety of Antimicrobials for Postexposure Prophylaxis and Treatment of Anthrax: A Review
Authors: Parker Corinne M , Karchmer Adolf W , Fisher Margaret C , Muhammad Kalimah M , Yu Patricia A
Published: October 2022

Background

Bacillus anthracis, the causative agent for anthrax, poses a potential bioterrorism threat and is capable of causing mass morbidity and mortality. Antimicrobials are the mainstay of postexposure prophylaxis (PEP) and treatment of anthrax. We conducted this safety review of 24 select antimicrobials to identify any new or emerging serious or severe adverse events (AEs) to help inform their risk–benefit evaluation for anthrax.

Methods

Twenty-four antimicrobials were included in this review. Tertiary data sources (e.g. Lactmed, Micromedex, REPROTOX) were reviewed for safety information and summarized to evaluate the known risks of these antimicrobials. PubMed was also searched for published safety information on serious or severe AEs with these antimicrobials; AEs that met inclusion criteria were abstracted and reviewed.

Results

A total of 1316 articles were reviewed. No consistent observations or patterns were observed among the abstracted AEs for a given antimicrobial; therefore, the literature review did not reveal evidence of new or emerging AEs that would add to the risk–benefit profiles already known from tertiary data sources.

Conclusions

The reviewed antimicrobials have known and/or potential serious or severe risks that may influence selection when recommending an antimicrobial for PEP or treatment of anthrax. Given the high fatality rate of anthrax, the risk–benefit evaluation favors use of these antimicrobials for anthrax. The potential risks of antimicrobials should not preclude these reviewed antimicrobials from clinical consideration for anthrax but rather guide appropriate antimicrobial selection and prioritization across different patient populations with risk mitigation measures as warranted.
Impact of Point-of-Care Testing on the Management of Sexually Transmitted Infections in South Africa: Evidence from the HVTN702 Human Immunodeficiency Virus Vaccine Trial
Authors: Asare Kwabena , Andine Tsion , Naicker Nivashnee , Dorward Jienchi , Singh Nishanta , Spooner Elizabeth , Andriesen Jessica , Osman Farzana , Ngcapu Sinaye , Vandormael Alain , Mindel Adrian , Abdool Karim Salim S , Bekker Linda-Gail , Gray Glenda , Corey Lawrence , Tomita Andrew , Garrett Nigel
Published: October 2022

Background

Alternative approaches to syndromic management are needed to reduce rates of sexually transmitted infections (STIs) in resource-limited settings. We investigated the impact of point-of-care (POC) versus central laboratory–based testing on STI treatment initiation and STI adverse event (STI-AE) reporting.

Methods

We used Kaplan-Meier and Cox regression models to compare times to treatment initiation and STI-AE reporting among HVTN702 trial participants in South Africa. Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were diagnosed POC at eThekwini clinic and in a central laboratory at Verulam/Isipingo clinics. All clinics used POC assays for Trichomonas vaginalis (TV) testing.

Results

Among 959 women (median age, 23 [interquartile range, 21–26] years), median days (95% confidence interval [95%CI]) to NG/CT treatment initiation and NG/CT-AE reporting were 0.20 (.16–.25) and 0.24 (.19–.27) at eThekwini versus 14.22 (14.12–15.09) and 15.12 (13.22–21.24) at Verulam/Isipingo (all P < .001). Median days (95%CI) to TV treatment initiation and TV-AE reporting were 0.17 (.12–.27) and 0.25 (.20–.99) at eThekwini versus 0.18 (.15–.2) and 0.24 (.15–.99) at Verulam/Isipingo (all P > .05). Cox regression analysis revealed that NG/CT treatment initiation (adjusted hazard ratio [aHR], 39.62 [95%CI, 15.13–103.74]) and NG/CT-AE reporting (aHR, 3.38 [95%CI, 2.23–5.13]) occurred faster at eThekwini versus Verulam/Isipingo, while times to TV treatment initiation (aHR, 0.93 [95%CI, .59–1.48]) and TV-AE reporting (aHR, 1.38 [95%CI, .86–2.21]) were similar.

Conclusions

POC testing led to prompt STI management with potential therapeutic and prevention benefits, highlighting its utility as a diagnostic tool in resource-limited settings.
Successful treatment of suspected early form of chronic Chagas cardiomyopathy: a case report
Authors: Lu Nelson , Werry Denise , Chapman Michael , Morshed Muhammad , Ndao Momar , Mirzanejad Yazdan
Published: October 2022

Background

Chagas disease, caused by the protozoan Trypanosoma cruzi, is the most common parasitic aetiology of non-ischaemic cardiomyopathy in the Americas, causing significant morbidity and mortality. The clinical spectrum ranges from early asymptomatic disease to severe cardiac manifestations including dilated cardiomyopathy, heart failure, dysrhythmias, conduction abnormalities, thromboembolism, and sudden death.

Case summary

We present a case of Chagas disease in a 75-year-old patient originally from El Salvador who presented to our Canadian tertiary centre with heart failure and atrial fibrillation/flutter. The patient had dilated cardiomyopathy with severely reduced systolic function, which was thought to be early Chagas cardiomyopathy after confirmatory positive serologies for T. cruzi. The patient demonstrated significant clinical improvement and recovery of systolic function with benznidazole therapy that was sustained up to 12 months on follow up.

Discussion

The American Heart Association recommends considering treatment of early chronic Chagas cardiomyopathy with anti-trypanosomal therapy. Our case highlights the importance of multidisciplinary collaboration in the diagnosis of early Chagas cardiomyopathy and critical timing of benznidazole, as effectiveness is limited in late disease due to myocardial cell-death programme. Although the historical BENEFIT study is known to not have shown mortality reduction, we advocate that the significant reduction in cardiovascular-related hospitalizations should be considered for symptomatic patients with early Chagas cardiomyopathy with the potential benefit of improving cardiac function and avoiding need for heart transplantation.
Predictors of mood or anxiety problems among transgender individuals seeking hormone therapy
Authors: Strenth Chance R , Pagels Patti , SoRelle Jeffrey A , Gonzalez Leo , Day Philip G , Gimpel Nora E , Levy Kamugisha Emily I , Moore Rachel M , Arnold Elizabeth Mayfield
Published: October 2022

Background

Mental health needs of transgender individuals can be complex with individual, social, and medical factors impacting symptoms. This study examines predictors of mood or anxiety problems among transgender individuals seeking hormone therapy (HT).

Methods

A retrospective chart review was conducted at 2 clinics providing gender-affirming HT. Cross-sectional data from initial patient encounters (N = 311) were used in this study. Bivariate correlations and multiple logistic regression analyses were carried out.

Results

Transgender women (TW) were 2.2 times more likely to have mood or anxiety problems while transgender men (TM) were 2.6 times more likely as the number of medical comorbidities increased. For both TW and TM, White race significantly increased the likelihood of mood or anxiety problems. Neither previous nor current HT were associated with mood or anxiety problems for TW and TM. However, receiving multiple gender-affirming procedures decreased the likelihood of mood or anxiety problems for TM.

Conclusions

Gender-affirming care and addressing comorbidities can be important aspects of mental health needs for transgender individuals.
High-resolution mapping reveals hotspots and sex-biased recombination inPopulus trichocarpa
Authors: Abeyratne Chanaka Roshan , Macaya-Sanz David , Zhou Ran , Barry Kerrie W , Daum Christopher , Haiby Kathy , Lipzen Anna , Stanton Brian , Yoshinaga Yuko , Zane Matthew , Tuskan Gerald A , DiFazio Stephen P
Published: October 2022

Fine-scale meiotic recombination is fundamental to the outcome of natural and artificial selection. Here, dense genetic mapping and haplotype reconstruction were used to estimate recombination for a full factorial Populus trichocarpa cross of 7 males and 7 females. Genomes of the resulting 49 full-sib families (N = 829 offspring) were resequenced, and high-fidelity biallelic SNP/INDELs and pedigree information were used to ascertain allelic phase and impute progeny genotypes to recover gametic haplotypes. The 14 parental genetic maps contained 1,820 SNP/INDELs on average that covered 376.7 Mb of physical length across 19 chromosomes. Comparison of parental and progeny haplotypes allowed fine-scale demarcation of cross-over regions, where 38,846 cross-over events in 1,658 gametes were observed. Cross-over events were positively associated with gene density and negatively associated with GC content and long-terminal repeats. One of the most striking findings was higher rates of cross-overs in males in 8 out of 19 chromosomes. Regions with elevated male cross-over rates had lower gene density and GC content than windows showing no sex bias. High-resolution analysis identified 67 candidate cross-over hotspots spread throughout the genome. DNA sequence motifs enriched in these regions showed striking similarity to those of maize, Arabidopsis, and wheat. These findings, and recombination estimates, will be useful for ongoing efforts to accelerate domestication of this and other biomass feedstocks, as well as future studies investigating broader questions related to evolutionary history, perennial development, phenology, wood formation, vegetative propagation, and dioecy that cannot be studied using annual plant model systems.
4. Terms of the Contract
Authors: Devenney James
Published: October 2022

The Concentrate Questions and Answers series offers the best preparation for tackling exam questions. Each book includes typical questions, answer plans and suggested answers, author commentary, and other features. This chapter explores the terms of the contract. It contains questions and answers concerning express and implied terms, how terms are to be identified, and how they are to be classified in order to determine what consequences flow from their breach. The chapter also considers two key debates: the basis on which the courts imply terms into contracts, and whether the courts approach the classification of terms highlights a tension in the law between certainty and justice.
5. Exemption Clauses and Unfair Terms
Authors: Devenney James
Published: October 2022

The Concentrate Questions and Answers series offers the best preparation for tackling exam questions. Each book includes typical questions, answer plans and suggested answers, author commentary, and other features. This chapter focuses on the regulation of exclusion/exemption clauses and other potentially unfair terms. It discusses both common law (such as approaches to incorporation and interpretation) and statutory regulation (such as the Unfair Contract Terms Act 1977 and the Consumer Rights Act 2015). It also explores two key debates: the nature of an exemption clause, and the tension between freedom of contract and judicial and statutory intervention in the context of exemption clauses.
6. Misrepresentation
Authors: Devenney James
Published: October 2022

The Concentrate Questions and Answers series offers the best preparation for tackling exam questions. Each book includes typical questions, answer plans and suggested answers, author commentary, and other features. Misrepresentation is defined as a false statement of fact, made pre-contractually, which is intended to induce the representee to enter into a contract and which has that effect. If an actionable misrepresentation is found to exist a court will then need to consider the available remedies. This chapter considers the following issues relevant to answering any problem question on misrepresentation. Has there been a false statement of fact? Is there evidence of inducement? What type of misrepresentation has potentially been made? What remedies are potentially available? Has liability for misrepresentation been effectively excluded? Has there been a breach of contract?
7. Improper Pressure
Authors: Devenney James
Published: October 2022

The Concentrate Questions and Answers series offers the best preparation for tackling exam questions. Each book includes typical questions, answer plans and suggested answers, author commentary, and other features. This chapter focuses on the doctrines of undue influence and duress. Between the parties to a con-tract there are broadly two ways that a contract can be avoided for undue influence: through affirmative proof of undue influence or through raising the presumption of undue influence which is not rebutted. As regards duress, there are two main forms: physical and economic. The more common type is economic duress, which focuses on the illegitimate pressure exerted by the dominant party.
3. The Standard of Care in Negligence
Authors: Steele Jenny
Published: October 2022

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter introduces the reader to the fault principle or negligence standard, along with its positive and negative implications. This chapter first asks. ‘What is negligence?’. It covers the standard of care and, within this, it looks at the objective standard. The chapter goes on to explore the way in which professional skill and care are assessed in the medical context. It also considers reasonable risk-taking and the absence of evidence of fault.
5. Duty of Care: Applications
Authors: Steele Jenny
Published: October 2022

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter deals with particular applications of the duty of care concept that determine the boundaries of the tort. Various cases on duty of care are examined in terms of recognized categories relating to negligently inflicted psychiatric damage, ‘pure economic loss’, and negligence liability of public authorities. The chapter also considers the assumption of responsibility criterion developed from the case of Hedley Byrne v Heller [1964] AC 465, as well as applications of the ‘Caparo approach’ used in establishing whether a duty is owed. Finally, it looks at emerging organizing concepts which appear to span different categories of case law.
7. Defences to Negligence
Authors: Steele Jenny
Published: October 2022

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter explores three defences to negligence which are also defences to other torts: volenti non fit injuria or willing assumption of risk, the illegality defence (also known as ex turpi causa), and contributory negligence. In relation to contributory negligence, the chapter considers responsibility, which involves questions both of causal influence and of fault, before turning to a discussion of apportionment of responsibility between the parties, and proportionality. In relation to illegality, recent decisions of the Supreme Court are examined. Relevant provisions of the Law Reform (Contributory Negligence) Act 1945 are extracted, together with further extracts from significant cases.
15. Privacy
Authors: Steele Jenny
Published: October 2022

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter focuses on the emergence of a new action to protect privacy under the Human Rights Act 1998, with particular reference to unjustified publication of private information. It begins by considering whether privacy is a protected interest at common law and whether privacy must be recognized and given protection through the law of tort. It then examines the tools which have been used in the partial absorption of privacy as a protected interest in common law, citing the provisions of the Human Rights Act 1998 and Article 8 of the European Convention on Human Rights. The controversies surrounding disclosure of private information and the power of injunctions are also considered, along with the issue of intrusion as an invasion of privacy.
17. Breach of Statutory Duty
Authors: Steele Jenny
Published: October 2022

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter deals with the action for breach of statutory duty, an action in tort meant to remedy harm caused by a breach of the duty. It first considers the distinctiveness of the tort of breach of statutory duty, with particular reference to the question of whether the breach gives rise to liability at common law. It then looks at case law involving civil liability for breach of industrial safety, citing Groves v Wimborne (Lord) [1898] 2 QB 402 and its significance in the context of workplace injuries. It also discusses cases dealing with ‘social welfare’ legislation and ‘public law duties’ as well as civil liberties before concluding with an assessment of the effect of the restrictive approach to the action for breach of statutory duty on the tort of negligence.
18. Trespass to Land and Goods, and Conversion
Authors: Steele Jenny
Published: October 2022

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter considers a range of proprietary torts which protect against trespass to land and goods, as well as conversion which protects against interferences with goods (but not land). It considers the overlap in functions between conversion and property law, particularly in the available remedies such as recovery of the chattel and damages based both on value of the goods (if not recovered) and on consequential loss. The chapter first looks at non-deliberate trespass to land and the remedies available to the claimant. This is followed by a discussion on wrongful interference with goods. The chapter then presents a general definition of conversion and its distinctive features, and what interest in the chattels the claimant must have. Finally, it outlines a number of remedies available to the claimant in the case of conversion. Relevant court cases are cited where appropriate.
The fly homolog ofSUPT16H, a gene associated with neurodevelopmental disorders, is required in a cell-autonomous fashion for cell survival
Authors: Ma Mengqi , Zhang Xi , Zheng Yiming , Lu Shenzhao , Pan Xueyang , Mao Xiao , Pan Hongling , Chung Hyung-lok , Wang Hua , Guo Hong , Bellen Hugo J
Published: October 2022

SUPT16H encodes the large subunit of the FAcilitate Chromatin Transcription (FACT) complex, which functions as a nucleosome organizer during transcription. We identified two individuals from unrelated families carrying de novo missense variants in SUPT16H. The probands exhibit global developmental delay, intellectual disability, epilepsy, facial dysmorphism and brain structural abnormalities. We used Drosophila to characterize two variants: p.T171I and p.G808R. Loss of the fly ortholog, dre4, causes lethality at an early developmental stage. RNAi-mediated knockdown of dre4 in either glia or neurons causes severely reduced eclosion and longevity. Tissue-specific knockdown of dre4 in the eye or wing leads to the loss of these tissues, whereas overexpression of SUPT16H has no dominant effect. Moreover, expression of the reference SUPT16H significantly rescues the loss-of-function phenotypes in the nervous system as well as wing and eye. In contrast, expression of SUPT16H p.T171I or p.G808R rescues the phenotypes poorly, indicating that the variants are partial loss-of-function alleles. While previous studies argued that the developmental arrest caused by loss of dre4 is due to impaired ecdysone production in the prothoracic gland, our data show that dre4 is required for proper cell growth and survival in multiple tissues in a cell-autonomous manner. Altogether, our data indicate that the de novo loss-of-function variants in SUPT16H are indeed associated with developmental and neurological defects observed in the probands.
Impact of Crohn’s Disease Therapies on Histology in Randomized Controlled Trials: Systematic Review With Meta-analysis
Authors: Roseira Joana , Santiago Mafalda , Estevinho Maria Manuela , Moreira Paula , Alves Catarina , Danese Silvio , Peyrin-Biroulet Laurent , Dignass Axel , Feakins Roger , Magro Fernando
Published: October 2022

Background

The effectiveness of Crohn’s disease treatments for inducing histological outcomes has not been addressed systematically. We performed a systematic review and meta-analysis of randomized controlled trials in Crohn’s disease to assess the impact of therapies on mucosal histopathology.

Methods

Databases (MEDLINE, CENTRAL, Web of Science, EMBASE) were searched for randomized controlled trials including adult patients and evaluating histological outcomes. Risk of bias was evaluated using the Critical Appraisal Skills Programme. Histological outcomes, pooled frequencies, pooled odds ratios, and standard mean differences of the histological scores were compared between the intervention and placebo groups using a random-effects model.

Results

Out of 2070 records, 10 studies were included. The quality of the studies ranged from moderate to high, but they were clinically and methodologically diverse. All interventions were superior to placebo. Histological response was achieved by 68% of patients, and 38% achieved remission. Pooled odds ratio for histological remission in patients receiving intervention vs placebo was 4.14 (95% CI, 2.28-7.50; I2 0%; P < .01). Heterogeneity in histological response estimates was significant, and subgroup analysis of the odds ratio results was limited by the low number of studies per group. The standard mean difference of histological scores was higher for patients receiving intervention in both induction and maintenance studies (−2.95; 95% CI, −4.17 to −1.74; I2 83% P < .00; and −2.58; 95% CI, −3.89 to −1.27; I2 56% P < .00).

Conclusions

Crohn’s disease therapies are effective for achieving histological outcomes. Adherence to recently published consensus on histopathology harmonization assessment in Crohn’s disease would facilitate adequate comparison between studies in the future.
Integrating Radiomics With Clinicoradiological Scoring Can Predict High-Risk Patients Who Need Surgery in Crohn’s Disease: A Pilot Study
Authors: Chirra Prathyush , Sharma Anamay , Bera Kaustav , Cohn H Matthew , Kurowski Jacob A , Amann Katelin , Rivero Marco-Jose , Madabhushi Anant , Lu Cheng , Paspulati Rajmohan , Stein Sharon L , Katz Jeffrey A , Viswanath Satish E , Dave Maneesh
Published: October 2022

Background

Early identification of Crohn’s disease (CD) patients at risk for complications could enable targeted surgical referral, but routine magnetic resonance enterography (MRE) has not been definitively correlated with need for surgery. Our objective was to identify computer-extracted image (radiomic) features from MRE associated with risk of surgery in CD and combine them with clinical and radiological assessments to predict time to intervention.

Methods

This was a retrospective single-center pilot study of CD patients who had an MRE within 3 months prior to initiating medical therapy. Radiomic features were extracted from annotated terminal ileum regions on MRE and combined with clinical variables and radiological assessment (via Simplified Magnetic Resonance Index of Activity scoring for wall thickening, edema, fat stranding, ulcers) in a random forest classifier. The primary endpoint was high- and low-risk groups based on need for surgery within 1 year of MRE. The secondary endpoint was time to surgery after treatment.

Results

Eight radiomic features capturing localized texture heterogeneity within the terminal ileum were significantly associated with risk of surgery within 1 year of treatment (P < .05); yielding a discovery cohort area under the receiver-operating characteristic curve of 0.67 (n = 50) and validation cohort area under the receiver-operating characteristic curve of 0.74 (n = 23). Kaplan-Meier analysis of radiomic features together with clinical variables and Simplified Magnetic Resonance Index of Activity scores yielded the best hazard ratio of 4.13 (P = (7.6 × 10-6) and concordance index of 0.71 in predicting time to surgery after MRE.

Conclusions

Radiomic features on MRE may be associated with risk of surgery in CD, and in combination with clinicoradiological scoring can yield an accurate prognostic model for time to surgery.
Global Bifurcation of Capillary-Gravity Water Waves With Overhanging Profiles and Arbitrary Vorticity
Authors: Wahlén Erik , Weber Jörg
Published: October 2022

We study two-dimensional periodic capillary-gravity water waves propagating at the free surface of water in a flow with arbitrary, prescribed vorticity over a flat bed. Using conformal mappings and a new reformulation of Bernoulli’s equation, the problem is equivalently cast into the form “identity plus compact”, which is amenable to Rabinowitz’s global bifurcation theorem, while no restrictions on the geometry of the surface profile and no assumptions regarding the absence of stagnation points in the flow have to be made. Within the scope of this new formulation, local curves and global families of solutions, bifurcating from laminar flows with a flat surface, are constructed.
The acquisition of transferable extrachromosomal fec operon is associated with a cefiderocol MIC increase in Enterobacterales
Authors: Kocer Kaan , Boutin Sébastien , Heeg Klaus , Nurjadi Dennis
Published: October 2022

Background

Cefiderocol is a novel siderophore cephalosporin active against MDR Gram-negative bacilli, including MBL-harbouring Enterobacterales. The detection of multiple cefiderocol-resistant blaVIM-carrying Enterobacterales isolates (MIC = 4 mg/L) from a single patient suggested an additional, potentially transferable, resistance determinant as blaVIM typically does not elevate cefiderocol MIC above the resistance threshold.

Methods

Transfer of a mobile genetic element was performed in liquid mating experiments. All donor isolates and transconjugants were characterized by short-read WGS to identify potential resistance determinants. mRNA expression of siderophore receptors was determined by quantitative RT–PCR. Validation was performed by transformation. Antibiotic susceptibility was determined by broth microdilution.

Results

Liquid mating experiments indicated the presence of transferable resistance determinants. Comparative genomic analysis of the clinical isolates and their respective transconjugants revealed the transfer of an accessory fec operon (fecABCDEIR). Transformation of the fec operon-containing vector into a TOP10 Escherichia coli led to an elevation of the cefiderocol MIC by at least 16-fold. Higher expression of fecA as a proxy for the fec operon mRNA expression was associated with phenotypic cefiderocol resistance. Both VIM and the accessory fec operon contribute to the elevation of cefiderocol MIC beyond the resistance threshold. The acquisition of an accessory fec operon via liquid mating confers phenotypic cefiderocol resistance in both E. coli J53 and Pseudomonas aeruginosa PAO1, indicating a broad-host-range nature of this mobile resistance determinant.

Conclusions

The emergence of a transferable cefiderocol resistance determinant without prior exposure to the substance is worrisome and should be monitored closely.
A survey of pregnant patients’ perspectives on the implementation of artificial intelligence in clinical care
Authors: Armero William , Gray Kathryn J , Fields Kara G , Cole Naida M , Bates David W , Kovacheva Vesela P
Published: October 2022

Objective

To evaluate and understand pregnant patients’ perspectives on the implementation of artificial intelligence (AI) in clinical care with a focus on opportunities to improve healthcare technologies and healthcare delivery.

Materials and Methods

We developed an anonymous survey and enrolled patients presenting to the labor and delivery unit at a tertiary care center September 2019–June 2020. We investigated the role and interplay of patient demographic factors, healthcare literacy, understanding of AI, comfort levels with various AI scenarios, and preferences for AI use in clinical care.

Results

Of the 349 parturients, 57.6% were between the ages of 25–34 years, 90.1% reported college or graduate education and 69.2% believed the benefits of AI use in clinical care outweighed the risks. Cluster analysis revealed 2 distinct groups: patients more comfortable with clinical AI use (Pro-AI) and those who preferred physician presence (AI-Cautious). Pro-AI patients had a higher degree of education, were more knowledgeable about AI use in their daily lives and saw AI use as a significant advancement in medicine. AI-Cautious patients reported a lack of human qualities and low trust in the technology as detriments to AI use.

Discussion

Patient trust and the preservation of the human physician-patient relationship are critical in moving forward with AI implementation in healthcare. Pregnant individuals are cautiously optimistic about AI use in their care.

Conclusion

Our findings provide insights into the status of AI use in perinatal care and provide a platform for driving patient-centered innovations.
Analysis of singular values in a 3D joint inversion problem of MMT and MCSEM data
Authors: da Silva Pinheiro Jéssica Larissa , Correa Silva Marcos Welby , Rao Ying
Published: October 2022

Single value decomposition (SVD) is a mathematical method of decomposing a matrix into three other matrices that have very important properties of the original matrix. One of these matrices provides us with the singular values of the original matrix. By analysing these singular values, we can determine whether an inverse problem has an ambiguous solution or whether the solution is stable. With this analysis we can also check whether the estimated solution gives an exact fit to the data, find out which combinations of parameters can be determined by observations and which cannot, and more. In this work, SVD was applied to assess the feasibility of a joint 3D inversion of marine magnetotelluric method (MMT) and marine controlled source electromagnetic method (MCSEM) data, as these methods should theoretically provide complementary information. The singular values were generated from the Hessian matrix of each method and from the joint implementation, and we compared them by considering the null space of each method. The analysis of the singular values proved to be an important step before the iterative inversion process, indicating the feasibility of the inversion without spending much time. However, we still need to spend the time to calculate the Jacobian and Hessian matrices.
Graph-based pan-genomes: increased opportunities in plant genomics
Authors: Wang Shuo , Qian Yong-Qing , Zhao Ru-Peng , Chen Ling-Ling , Song Jia-Ming
Published: October 2022

Due to the development of sequencing technology and the great reduction in sequencing costs, an increasing number of plant genomes have been assembled, and numerous genomes have revealed large amounts of variations. However, a single reference genome does not allow the exploration of species diversity, and therefore the concept of pan-genome was developed. A pan-genome is a collection of all sequences available for a species, including a large number of consensus sequences, large structural variations, and small variations including single nucleotide polymorphisms and insertions/deletions. A simple linear pan-genome does not allow these structural variations to be intuitively characterized, so graph-based pan-genomes have been developed. These pan-genomes store sequence and structural variation information in the form of nodes and paths to store and display species variation information in a more intuitive manner. The key role of graph-based pan-genomes is to expand the coordinate system of the linear reference genome to accommodate more regions of genetic diversity. Here, we review the origin and development of graph-based pan-genomes, explore their application in plant research, and further highlight the application of graph-based pan-genomes for future plant breeding.
Explaining migrant integration policies: A comparative study across 56 countries
Authors: Solano Giacomo , De Coninck David
Published: October 2022

This article provides novel insights into the main factors associated with integration policies at the national level. Existing literature has analysed specific factors in Western countries, while a comprehensive, theoretically informed, and up-to-date overview is missing, especially regarding non-Western countries. This article fills this gap by combining 2014 and 2019 Migrant Integration Policy Index data on integration policies in 56 countries—including non-Western countries—with publicly available international data on migration and asylum trends, economic conditions, and public opinion on migration. Building upon existing literature, we introduce three perspectives: evidence-based, institutionalist, and partisan perspectives. The evidence-based perspective assumes that policy-makers act based on objective factors related to the policy issue (e.g. the number of migrants). The institutionalist perspective points to the relevance of institutional conditions, such as labour markets and welfare institutions. The partisan perspective refers to the role of political ideologies and attitudes in public opinion and in the media. Results suggest that factors related to the institutionalist perspective play the most critical role, alongside factors linked to the partisan perspective. However, the results provide evidence for all three perspectives. Migrant integration policies are associated with several factors: the number of asylum applications and the number of refugees (evidence-based perspective); GDP (per capita) and welfare expenditure (institutionalist perspective); political ideology; and public opinion (partisan perspective).
Magnetic braking saturates: evidence from the orbital period distribution of low-mass detached eclipsing binaries from ZTF
Authors: El-Badry Kareem , Conroy Charlie , Fuller Jim , Kiman Rocio , van Roestel Jan , Rodriguez Antonio C , Burdge Kevin B
Published: October 2022

We constrain the orbital period (Porb) distribution of low-mass detached main-sequence eclipsing binaries (EBs) with light-curves from the Zwicky Transient Facility (ZTF), which provides a well-understood selection function and sensitivity to faint stars. At short periods (Porb ≲ 2 d), binaries are predicted to evolve significantly due to magnetic braking (MB), which shrinks orbits and ultimately brings detached binaries into contact. The period distribution is thus a sensitive probe of MB. We find that the intrinsic period distribution of low-mass (0.1 ≲ M1/M⊙ < 0.9) binaries is basically flat (${\rm d}N/{\rm d}P_{\rm orb} \propto P_{\rm orb}^0$) from Porb = 10 d down to the contact limit. This is strongly inconsistent with predictions of classical MB models based on the Skumanich relation, which are widely used in binary evolution calculations and predict ${\rm d}N/{\rm d}P_{\rm orb} \propto P_{\rm orb}^{7/3}$ at short periods. The observed distributions are best reproduced by models in which the magnetic field saturates at short periods with a MB torque that scales roughly as $\dot{J}\propto P_{\rm orb}^{-1}$, as opposed to $\dot{J} \propto P_{\rm orb}^{-3}$ in the standard Skumanich law. We also find no significant difference between the period distributions of binaries containing fully and partially convective stars. Our results confirm that a saturated MB law, which was previously found to describe the spin-down of rapidly rotating isolated M dwarfs, also operates in tidally locked binaries. We advocate using saturated MB models in binary evolution calculations. Our work supports previous suggestions that MB in cataclysmic variables (CVs) is much weaker than assumed in the standard evolutionary model, unless mass transfer leads to significant additional angular momentum loss in CVs.
Launch of a sounding balloon for horizontal and vertical modelling of ALAN propagation in the atmosphere
Authors: Cavazzani S , Fiorentin P , Bettanini C , Bartolomei M , Bertolin C , Ortolani S , Bertolo A , Binotto R , Olivieri L , Aboudan A , Colombatti G
Published: October 2022

The propagation of light radiation in the atmosphere is a topic that needs to be properly analysed to mitigate its negative influence on astronomical observations. This work describes a novel approach for evaluating atmospheric propagation of artificial light at night (ALAN), emphasizing the dependence on altitude and aerosols. It is based on an innovative experiment using a sounding balloon equipped with two sky-quality meters (SQM): one vertically pointed at 30° (SQM-V) and the other horizontally at 90° (SQM-H) from the zenith. The system was launched during astronomical night conditions from an area of the Italian Apennines with low ground light emission and crossed the Tuscan sky, observing the vertical and horizontal ALAN propagation. The data analysis of the two SQMs and their georeferentiation through altitude and trajectory reconstruction allows us to model the propagation of light in the experimental field of view from a few hundred metres up to an altitude of about 30 km. In this work, the main focus is given to the tropospheric part of the atmosphere up to 12 500 m: the processed data are used to validate a theoretical model taking into account the altitude, course of the balloon, atmospheric composition, and population of the cities overflown by the balloon, obtaining a correlation of 0.85 with SQM-H and 0.91 with SQM-V. The magnitude values of close to 21.5 $\mathrm{mag\, arcsec}^{-2}$ measured by SQM-V at 2000 m are an important experimental result for evaluating the influence of aerosols and altitude on ALAN propagation.
A case of glucocorticoid-resistant adult Still’s disease complicated by pulmonary hypertension and interstitial lung disease
Authors: Kusaka Katsuhide , Miyagawa Ippei , Kosaka Shunpei , Matsunaga Satsuki , Nakayamada Shingo , Tanaka Yoshiya
Published: October 2022

Adult Still’s disease (ASD) is rarely complicated by pulmonary hypertension (PH). A 76-year-old woman experienced ASD relapse with repeated exacerbation of PH and interstitial lung disease. Although she had been treated with immunosuppressive agents and pulmonary vasodilators, the ASD relapsed with fever, rash, increased inflammatory responses and exacerbated interstitial lung disease, and PH. The pathology of PH appeared to encompass groups 1 [pulmonary arterial hypertension (PAH)], 1ʹ [pulmonary veno-occlusive disease (PVOD)], and 3. Remission induction therapy with high-dose glucocorticoid and tocilizumab was administered, and switching or adding pulmonary vasodilators was also attempted. As the disease activity of ASD decreased, the mean pulmonary arterial pressure and pulmonary vascular resistance improved. PH is an extremely rare form of organ dysfunction in individuals with ASD. Like other systemic autoimmune diseases, PH (PAH or PVOD) can determine the prognosis of ASD. Because of PH’s rarity, it is important to sufficiently evaluate its pathology, considering the possibility that PH is not clinically classified as PAH (group 1), and to administer immunosuppressive therapy and vasodilators according to the pathology.
The Mycobacterium tuberculosis Ku C-terminus is a multi-purpose arm for binding DNA and LigD and stimulating ligation
Authors: Sowa Dana J , Warner Monica M , Tetenych Andriana , Koechlin Lucas , Balari Pardis , Rascon Perez Jose Pablo , Caba Cody , Andres Sara N
Published: October 2022

Bacterial non-homologous end joining requires the ligase, LigD and Ku. Ku finds the break site, recruits LigD, and then assists LigD to seal the phosphodiester backbone. Bacterial Ku contains a core domain conserved with eukaryotes but has a unique C-terminus that can be divided into a minimal C-terminal region that is conserved and an extended C-terminal region that varies in sequence and length between species. Here, we examine the role of Mycobacterium tuberculosis Ku C-terminal variants, where we removed either the extended or entire C-terminus to investigate the effects on Ku–DNA binding, rates of Ku-stimulated ligation, and binding affinity of a direct Ku–LigD interaction. We find that the extended C-terminus limits DNA binding and identify key amino acids that contribute to this effect through alanine-scanning mutagenesis. The minimal C-terminus is sufficient to stimulate ligation of double-stranded DNA, but the Ku core domain also contributes to stimulating ligation. We further show that wildtype Ku and the Ku core domain alone directly bind both ligase and polymerase domains of LigD. Our results suggest that Ku-stimulated ligation involves direct interactions between the Ku core domain and the LigD ligase domain, in addition to the extended Ku C-terminus and the LigD polymerase domain.
Global mitigation efforts cannot neglect emerging emitters
Authors: Cui Can , Guan Dabo , Wang Daoping , Meng Jing , Chemutai Vicky , Brenton Paul , Zhang Shaohui , Shan Yuli , Zhang Qiang , Davis Steven J
Published: October 2022

International efforts to avoid dangerous climate change have historically focused on reducing energy-related CO2 emissions from countries with either the largest economies (e.g. the EU and the USA) and/or the largest populations (e.g. China and India). However, in recent years, emissions have surged among a different and much less-examined group of countries, raising concerns that a next generation of high-emitting economies will obviate current mitigation targets. Here, we analyse the trends and drivers of emissions in each of the 59 countries where emissions in 2010–2018 grew faster than the global average (excluding China and India), project their emissions under a range of longer-term energy scenarios and estimate the costs of decarbonization pathways. Total emissions from these ‘emerging emitters’ reach as much as 7.5 GtCO2/year in the baseline 2.5° scenario—substantially greater than the emissions from these regions in previously published scenarios that would limit warming to 1.5°C or even 2°C. Such unanticipated emissions would in turn require non-emitting energy deployment from all sectors within these emerging emitters, and faster and deeper reductions in emissions from other countries to meet international climate goals. Moreover, the annual costs of keeping emissions at the low level are in many cases 0.2%–4.1% of countries’ gross domestic production, pointing to potential trade-offs with poverty-reduction goals and/or the need for economic support and low-carbon technology transfer from historically high-emitting countries. Our results thus highlight the critical importance of ramping up mitigation efforts in countries that to this point have been largely ignored.
Sick leave during pregnancy and occupational factors: a systematic review
Authors: Henrotin J B , Gulisano F
Published: October 2022

Background

The reported prevalence of sick leave (SL) during pregnancy is high among European pregnant workers (PW). The causes of SL during pregnancy are complex, and further research is necessary to explain their occurrence.

Aims

Summarize the evidence for an association between occupational risks for pregnancy and SL.

Methods

A systematic review was conducted by two independent reviewers using PRISMA guidelines. Two databases (Pubmed, Embase) were interrogated between January 1990 and November 2021. The search question integrated key terms according to the PICOS acronym (free terms, MeSH, EMTREE). The quality of the selected studies was assessed according to the Methodological Index for Non-randomized Studies score.

Results

This review assessed 11 epidemiological studies. Overall, the mean Methodological Index for Non-Randomized Studies score was 11, indicating moderate study quality. The results of the limited number of studies showed limited evidence for associations between psychosocial and physical work-related risk factors and the occurrence of SL among PW. However, this assessment was strengthened by the observation in several studies of a dose–response relationship between the number of occupational risks during pregnancy and SL.

Conclusions

The analysis of this review implicates PW’S exposure to occupational risks in the occurrence of SL. However, the few studies that support this conclusion have provided weak evidence; thus, further research is necessary.