bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of cumulative childhood exposure to neighbourhood socioeconomic disadvantage on school performance—a register-based study on neighbourhoods, schools, and siblings
Authors: Tarkiainen Lasse , Kemppainen Teemu , Lahtinen Hannu , Bernelius Venla , Martikainen Pekka
Published: September 2023

Several studies show that exposure to neighbourhood disadvantage predicts poorer educational outcomes among adolescents. Selective sorting into neighbourhoods, other unobserved childhood family characteristics, and failing to account for other relevant social contexts such as schools inhibit strong causal inference from the associations reported in previous studies. Based on longitudinal register data on the total population of Finnish children in major cities, we studied the extent to which variation in grade point average (GPA) was attributable to schools, neighbourhoods, and families. We also sought to determine whether exposure to neighbourhood disadvantage predicted GPA after accounting for non-random selection into neighbourhoods by comparing siblings with differential exposure to neighbourhoods. Overall, we observed no effect of neighbourhood disadvantage on GPA after accounting for observed and unobserved family characteristics in the general population. However, we did observe a non-negligible but not statistically significant effect of neighbourhood disadvantage among children of parents with only basic education. Family factors accounted for most of the variation in GPA, and only around 1 per cent of the variance was attributable to the neighbourhood. This weak relevance of the neighbourhood to educational outcomes may reflect the success of educational and other social policies limiting the emergence of neighbourhood effects.
Atrial fibrillation cryoablation is an effective day case treatment: the UK PolarX vs. Arctic Front Advance experience
Authors: Honarbakhsh Shohreh , Martin Claire A , Mesquita Joao , Herlekar Rahul , Till Richard , Srinivasan Neil T , Duncan Edward , Leong Fong , Dulai Rajdip , Veasey Rick , Panikker Sandeep , Paisey John , Ramgopal Balasubramanian , Das Moloy , Ahmed Wissam , Sahu Jonathan , Earley Mark J , Finlay Malcolm C , Schilling Richard J , Hunter Ross J
Published: September 2023

Aims

Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation for atrial fibrillation (AF). There are limited data on the PolarX Cryoballoon. The study aimed to establish the safety, efficacy, and feasibility of same day discharge for Cryoballoon PVI.

Methods and results

Multi-centre study across 12 centres. Procedural metrics, safety profile, and procedural efficacy of the PolarX Cryoballoon with the Arctic Front Advance (AFA) Cryoballoon were compared in a cohort large enough to provide definitive comparative data. A total of 1688 patients underwent PVI with cryoablation (50% PolarX and 50% AFA). Successful PVI was achieved with 1677 (99.3%) patients with 97.2% (n = 1641) performed as day case procedures with a complication rate of <1%. Safety, procedural metrics, and efficacy of the PolarX Cryoballoon were comparable with the AFA cohort. The PolarX Cryoballoon demonstrated a nadir temperature of −54.6 ± 7.6°C, temperature at 30 s of −38.6 ± 7.2°C, time to −40°C of 34.1 ± 13.7 s, and time to isolation of 49.8 ± 33.2 s. Independent predictors for achieving PVI included time to reach −40°C [odds ratio (OR) 1.34; P < 0.001] and nadir temperature (OR 1.24; P < 0.001) with an optimal cut-off of ≤34 s [area under the curve (AUC) 0.73; P < 0.001] and nadir temperature of ≤−54.0°C (AUC 0.71; P < 0.001), respectively.

Conclusions

This large-scale UK multi-centre study has shown that Cryoballoon PVI is a safe, effective day case procedure. PVI using the PolarX Cryoballoon was similarly safe and effective as the AFA Cryoballoon. The cryoablation metrics achieved with the PolarX Cryoballoon were different to that reported with the AFA Cryoballoon. Modified cryoablation targets are required when utilizing the PolarX Cryoballoon.
Insight into the relationship between resting heart rate and atrial fibrillation: a Mendelian randomization study
Authors: Klevjer Marie , Rasheed Humaira , Romundstad Pål R , Madssen Erik , Brumpton Ben M , Bye Anja
Published: September 2023

Aims

A low resting heart rate (RHR) implies a more efficient heart function and a lower risk of cardiovascular disease. However, observational studies have reported a U-shaped association between RHR and atrial fibrillation (AF). In contrast, Mendelian randomization (MR) studies have found an inverse causal association between RHR and AF. Hence, the causal nature of the relationship is not clear. The aim is to investigate the causal association and its shape between RHR on AF using linear and non-linear MR (NLMR).

Methods and results

Linear and non-linear MR were performed on individual-level data in the Trøndelag Health Study (HUNT) and UK Biobank (UKB). HUNT consists of 69 155 individuals with 7,062 AF cases, while UKB provides data on 431 852 individuals with 20 452 AF cases. The linear MR found an inverse relationship between RHR and AF with an OR = 0.95 [95% confidence interval (CI): 0.93–0.98] and OR = 0.96 (95% CI: 0.95–0.97) per unit decrease in RHR in HUNT and UKB, respectively. The NLMR was supportive of an inverse linear relationship in both HUNT and UKB for RHR values <90 beats per minute (bpm). Several sensitivity analyses were also consistent.

Conclusion

In contrast with the current observational knowledge of RHR and AF, an inverse causal association between RHR and AF was demonstrated in both linear and non-linear MR for RHR values up to 90 bpm. Further exploring the underlying mechanisms of the genetic instrument for RHR may shed light on whether pleiotropy is biasing this association.
Long-term evolution of antibiotic tolerance in Pseudomonas aeruginosa lung infections
Authors: Ghoul Melanie , Andersen Sandra B , Marvig Rasmus L , Johansen Helle K , Jelsbak Lars , Molin Søren , Perron Gabriel , Griffin Ashleigh S
Published: September 2023

Pathogenic bacteria respond to antibiotic pressure with the evolution of resistance but survival can also depend on their ability to tolerate antibiotic treatment, known as tolerance. While a variety of resistance mechanisms and underlying genetics are well characterized in vitro and in vivo, an understanding of the evolution of tolerance, and how it interacts with resistance in situ is lacking. We assayed for tolerance and resistance in isolates of Pseudomonas aeruginosa from chronic cystic fibrosis lung infections spanning up to 40 years of evolution, with 3 clinically relevant antibiotics: meropenem, ciprofloxacin, and tobramycin. We present evidence that tolerance is under positive selection in the lung and that it can act as an evolutionary stepping stone to resistance. However, by examining evolutionary patterns across multiple patients in different clone types, a key result is that the potential for an association between the evolution of resistance and tolerance is not inevitable, and difficult to predict.
Host learning selects for the coevolution of greater egg mimicry and narrower antiparasitic egg-rejection thresholds
Authors: Xu Kuangyi , Servedio Maria R , Winnicki Sarah K , Moskat Csaba , Hoover Jeffrey P , Turner Abbigail M , Hauber Mark E
Published: September 2023

Egg rejection is an effective and widespread antiparasitic defense to eliminate foreign eggs from the nests of hosts of brood parasitic birds. Several lines of observational and critical experimental evidence support a role for learning by hosts in the recognition of parasitic versus own eggs; specifically, individual hosts that have had prior or current experience with brood parasitism are more likely to reject foreign eggs. Here we confirm experimentally the role of prior experience in altering subsequent egg-rejection decisions in the American robin Turdus migratorius, a free-living host species of an obligate brood parasite, the brown-headed cowbird Molothrus ater. We then model the coevolutionary trajectory of both the extent of mimicry of host eggs by parasitic eggs and the host’s egg rejection thresholds in response to an increasing role of learning in egg recognition. Critically, with more learning, we see the evolution of both narrower (more discriminating) rejection thresholds in hosts and greater egg mimicry in parasites. Increasing host clutch size (number of eggs/nest) and increasing parasite load (parasitism rate) also have narrowing effects on the egg-rejection threshold. Together, these results suggest that learning from prior experience with egg rejection may play an important role in the coevolution of egg-mimetic lineages of brood parasites and the refined egg rejection defenses of hosts.
Source-encoded waveform inversion in the Northern Hemisphere
Authors: Cui Congyue , Bachmann Etienne , Peter Daniel , Liu Zhaolun , Tromp Jeroen
Published: September 2023

We use source-encoded waveform inversion to image Earth’s Northern Hemisphere. The encoding method is based on measurements of Laplace coefficients of stationary wavefields. By assigning to each event a unique frequency, we compute Fréchet derivatives for all events simultaneously based on one ‘super’ forward and one ‘super’ adjoint simulation for a small fraction of the computational cost of classical waveform inversion with the same data set. No cross-talk noise is introduced in the process, and the method does not require all events to be recorded by all stations. Starting from global model GLAD_M25, we performed 100 conjugate gradient iterations using a data set consisting of 786 earthquakes recorded by 9846 stations. Synthetic inversion tests show that we achieve good convergence based on this data set, and we see a consistent misfit reduction during the inversion. The new model, named SE100, has much higher spatial resolution than GLAD_M25, revealing details of the Yellowstone and Iceland hotspots, subduction beneath the Western United States and the upper mantle structure beneath the Arctic Ocean.
2. The social context of the legal profession
Authors: Herring Jonathan
Published: September 2023

This chapter looks at lawyers in a broad social context. Lawyers hold a position of privilege within society by virtue of their knowledge about the law. It explores why lawyers have this special status and the role that they play in the broader society. This is coming under challenge as a range of other individuals and groups seek to take on what might be traditionally seen as legal work. There is also a tension between the wish to maintain the integrity of the legal profession, while increasing access to it. The chapter shows that the legal profession is under challenge from a number of directions.
9. Negligence and lawyers
Authors: Herring Jonathan
Published: September 2023

This chapter examines the circumstances in which a barrister and solicitor can be sued in negligence or for breach of contract. Clients can sue a solicitor based on the law of contract, the law of fiduciary duty, and the law of negligence. In general, a client is going to face an uphill battle in suing a solicitor or barrister. In relation to a breach of contract, it can be difficult to establish the breach of reasonable skill. In relation to negligence, proving breach of a duty of care and the causation of a loss is problematic.
14. Lawyers’ social responsibilities
Authors: Herring Jonathan
Published: September 2023

This chapter examines the responsibilities that lawyers have to society and the greater good. While the professional codes tend to focus on duties to clients, there are some limited duties to the public good. These are found in the duties under the criminal law, and the broader duty to the court and justice system. Lawyers also recognise an obligation to the greater good by means of their pro bono work. However, this is not undertaken by every lawyer. A particularly topical issue is the extent to which duties to respond to the climate emergency should be balanced with their duties to clients. Some lawyers increasingly present a public profile as advocates for certain causes or political positions and this can create problems.
Development and validation of the Health Literacy Scale for community-dwelling older adults in Taiwan
Authors: Kuo Shu-Hsin , Liang Ming-Hao
Published: September 2023

Health literacy is a crucial factor in determining one’s health outcomes. Individuals with high health literacy possess the ability to access, comprehend, evaluate, and utilize health information to maintain, enhance, and advocate for good health. This study aimed to develop and validate a tool called the Health Literacy Questionnaire for Older Adults (HLQ-OA) specifically designed to assess the health literacy of community-dwelling older adults in Taiwan. The development of the HLQ-OA occurred in two phases. Firstly, a systematic literature review was conducted, followed by the evaluation of content validity and face validity through expert and older adult assessments. Subsequently, a cross-sectional study was carried out, involving a convenient sample of 481 older adults from community-dwelling long-term care stations. The final version of the HLQ-OA comprised 16 items that assessed four competencies associated with accessing, understanding, appraising, and applying health-related information. The HLQ-OA demonstrated excellent internal consistency, with an overall Cronbach’s α coefficient of 0.94. Additionally, the model fit indices indicated an acceptable fit: RMSEA = 0.046, GFI = 0.909, CFI = 0.945, TLI = 0.939. Furthermore, a high correlation was observed between the HLQ-OA and the HL-SF12 (r = 0.832). These findings support the reliability and validity of the HLQ-OA as a tool for assessing the health literacy of older adults. In conclusion, the HLQ-OA is a reliable and valid instrument that can be effectively utilized to measure the health literacy levels of older adults.
Why we need weather forecast analogues for marine ecosystems
Authors: Link J S , Thur S , Matlock G , Grasso M
Published: September 2023

Marine ecosystems face many consequential pressures. Yet, we lack an integrative and predictive capacity to understand how marine ecosystems will respond to the cumulative impacts of these pressures, including climate change. It is not enough to detect responses after the fact; it has become imperative to know in advance where major biological resources or hazards will occur, when they will peak, and how that will impact economic performance. Although forecasts exist for some components of marine ecosystems, these are disparate and suffer from a lack of coordination. There is a need for coordinated, cross-ecosystem scale, integrated, marine ecosystem predictions and synthesis products. The value proposition relative to the blue economy is quite high, positively influencing billions if not trillions of marine sector dollars.
Associations of maternal motor vehicle crashes during pregnancy with offspring’s neonatal birth outcomes
Authors: Chang Ya-Hui , Chien Yu-Wen , Chang Chiung-Hsin , Chen Ping-Ling , Lu Tsung-Hsueh , Hsu I-Lin , Li Chung-Yi
Published: September 2023

Background

Adverse events in fetuses are well researched but studies on the follow-up health outcomes of infants exposed to maternal motor vehicle crashes (MVCs) during pregnancy have yielded inconsistent results. This study aimed to investigate the association of maternal exposure to MVCs during pregnancy with the risk of adverse neonatal outcomes.

Methods

This population-based cohort study used data from birth notifications in Taiwan. A total of 19 277 offspring with maternal exposure to MVCs during pregnancy and 76 015 randomly selected comparison offspring without such exposure were selected. Neonatal adverse outcomes were identified from National Health Insurance medical claims data. Conditional logistic regression was used to estimate the unadjusted and adjusted odds ratios (aORs) of neonatal adverse outcomes.

Results

Offspring exposed to maternal MVCs during pregnancy had a higher risk of birth defects (aOR, 1.21; 95% CI, 1.04–1.41) than offspring without such exposure. This positive association was sustained with exposure to an MVC during the first or second trimester. A dose–response relationship (P = 0.0023) was observed between the level of injury severity and the risk of birth defects.

Conclusions

In the early stages of pregnancy, maternal exposure to MVCs may entail a risk of birth defects in the offspring. The potential mechanisms for the associations of maternal exposure to MVCs with birth defects need further investigation.
Communicating and understanding statistical measures when quantifying the between-group difference in competing risks
Authors: Wu Hongji , Zhang Chengfeng , Hou Yawen , Chen Zheng
Published: September 2023

Competing risks issues are common in clinical trials and epidemiological studies for patients in follow-up who may experience a variety of possible outcomes. Under such competing risks, two hazard-based statistical methods, cause-specific hazard (CSH) and subdistribution hazard (SDH), are frequently used to assess treatment effects among groups. However, the outcomes of the CSH-based and SDH-based methods have a close connection with the proportional hazards (CSH or SDH) assumption and may have an non-intuitive interpretation. Recently, restricted mean time lost (RMTL) has been used as an alternative summary measure for analysing competing risks, due to its clinical interpretability and robustness to the proportional hazards assumption. Considering the above approaches, we summarize the differences between hazard-based and RMTL-based methods from the aspects of practical interpretation, proportional hazards model assumption and the selection of restricted time points, and propose corresponding suggestions for the analysis of between-group differences under competing risks. Moreover, an R package ‘cRMTL’ and corresponding step-by-step guidance are available to help users for applying these approaches.
Rotavirus Genotypes in the Postvaccine Era: A Systematic Review and Meta-analysis of Global, Regional, and Temporal Trends by Rotavirus Vaccine Introduction
Authors: Amin Avnika B , Cates Jordan E , Liu Zihao , Wu Joanne , Ali Iman , Rodriguez Alexia , Panjwani Junaid , Tate Jacqueline E , Lopman Benjamin A , Parashar Umesh D
Published: September 2023

Background

Even moderate differences in rotavirus vaccine effectiveness against nonvaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal fluctuations underlie observed changes in genotype distributions is unclear.

Methods

We systematically reviewed studies reporting rotavirus genotypes from children <5 years of age globally between 2005 and 2023. We compared rotavirus genotypes between vaccine-introducing and nonintroducing settings globally and by World Health Organization (WHO) region, calendar time, and time since vaccine introduction.

Results

Crude pooling of genotype data from 361 studies indicated higher G2P[4], a nonvaccine genotype, prevalence in vaccine-introducing settings, both globally and by WHO region. This difference did not emerge when examining genotypes over time in the Americas, the only region with robust longitudinal data. Relative to nonintroducing settings, G2P[4] detections were more likely in settings with recent introduction (eg, 1–2 years postintroduction adjusted odds ratio [aOR], 4.39; 95% confidence interval [CI], 2.87–6.72) but were similarly likely in settings with more time elapsed since introduction, (eg, 7 or more years aOR, 1.62; 95% CI, .49–5.37).

Conclusions

When accounting for both regional and temporal trends, there was no substantial evidence of long-term vaccine-related selective pressures on circulating genotypes. Increased prevalence of G2P[4] may be transient after rotavirus vaccine introduction.
Exit from Nuremberg to the Hague: The Malabo Protocol and the Pan-African Road to Arusha
Authors: Ba Oumar
Published: September 2023

In adopting the Malabo Protocol and creating the African Court of Justice and Human Rights, the African Union has established the first ever regional court with international criminal jurisdiction. This milestone signals once again, the role of African institutions in creating and developing norms in international politics. Yet, both International Relations (IR) theories and debates and official narratives of the historiography of the international legal order tend to omit the sustained contributions of African states and institutions. Echoes of the African Union (AU)’s efforts to define and codify crimes that are of concern to its constituents can be found in the African states’ interventions at the International Law Commission during the 1980s and the negotiations that lead to the creation of the International Criminal Court (ICC) in the 1990s. This article argues that beyond the critique and skepticism about the Malabo Protocol and the AU’s agenda, there is a sustained vision and trajectory that underlies African agency in norms creation and attempts to usher in an international legal order that speaks more directly and equitably to the concerns of the continent. Ultimately, I propose a genealogy of those Pan-African visions for an embedded international justice system that provides a fundamental corrective to the Nuremberg to The Hague narrative.
Nitrofurantoin: what is the evidence for current UK guidance?
Authors: Kashouris Eleanor , Joseph Amelia , Lewis Tom
Published: September 2023

Three days of nitrofurantoin at 100 mg twice daily is recommended as first-line treatment for uncomplicated urinary tract infection (UTI) in evidence-based guidelines across the UK. A review of international guidelines shows that the evidence base has been interpreted in very different ways. UK guidelines are unusual in promoting short (3 day) courses, and we find little direct evidence to support this. Although ‘short’ courses of antibiotics for other agents may provide optimum balance between providing effective treatment whilst reducing selective pressure driving resistance amongst colonizing microbial flora, it remains unclear that course lengths can be extrapolated to nitrofurantoin. Three days of nitrofurantoin may indeed be a useful intervention in a large group of patients. However, without supporting evidence and because clinical response should be expected to vary widely, it is unclear that establishing and promoting an antibiotic duration for UTI is the best approach to optimizing prescribing in this important area.
NKG2A discriminates natural killer cells with a suppressed phenotype in pediatric acute leukemia
Authors: Ulvmoen Aina , Greiff Victor , Bechensteen Anne G , Inngjerdingen Marit
Published: September 2023

Natural killer (NK) cells are important for early tumor immune surveillance. In patients with hematological cancers, NK cells are generally functional deficient and display dysregulations in their receptor repertoires. Acute leukemia is the most common cancer in children, and we here performed a comparative phenotypic profiling of NK cells from B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients to identify aberrant NK cell phenotypes. NK cell phenotypes, maturation, and function were analyzed in matched bone marrow and blood NK cells from BCP-ALL patients at diagnosis, during treatment, and at end of treatment and compared with age-matched pediatric control subjects. Expression of several markers were skewed in patients, but with large interindividual variations. Undertaking a multiparameter approach, we found that high expression levels of NKG2A was the single predominant marker distinguishing NK cells in BCP-ALL patients compared with healthy control subjects. Moreover, naïve CD57−NKG2A NK cells dominated in BCP-ALL patients at diagnosis. Further, we found dysregulated expression of the activating receptor DNAM-1 in resident bone marrow CXCR6+ NK cells. CXCR6+ NK cells lacking DNAM-1 expressed NKG2A and had a tendency for lower degranulation activity. In conclusion, high expression of NKG2A dominates NK cell phenotypes from pediatric BCP-ALL patients, indicating that NKG2A could be targeted in therapies for this patient group.
Overview of approaches to estimate real-world disease progression in lung cancer
Authors: Amorrortu Rossybelle , Garcia Melany , Zhao Yayi , El Naqa Issam , Balagurunathan Yoganand , Chen Dung-Tsa , Thieu Thanh , Schabath Matthew B , Rollison Dana E
Published: September 2023

Background

Randomized clinical trials of novel treatments for solid tumors normally measure disease progression using the Response Evaluation Criteria in Solid Tumors. However, novel, scalable approaches to estimate disease progression using real-world data are needed to advance cancer outcomes research. The purpose of this narrative review is to summarize examples from the existing literature on approaches to estimate real-world disease progression and their relative strengths and limitations, using lung cancer as a case study.

Methods

A narrative literature review was conducted in PubMed to identify articles that used approaches to estimate real-world disease progression in lung cancer patients. Data abstracted included data source, approach used to estimate real-world progression, and comparison to a selected gold standard (if applicable).

Results

A total of 40 articles were identified from 2008 to 2022. Five approaches to estimate real-world disease progression were identified including manual abstraction of medical records, natural language processing of clinical notes and/or radiology reports, treatment-based algorithms, changes in tumor volume, and delta radiomics–based approaches. The accuracy of these progression approaches were assessed using different methods, including correlations between real-world endpoints and overall survival for manual abstraction (Spearman rank ρ = 0.61-0.84) and area under the curve for natural language processing approaches (area under the curve = 0.86-0.96).

Conclusions

Real-world disease progression has been measured in several observational studies of lung cancer. However, comparing the accuracy of methods across studies is challenging, in part, because of the lack of a gold standard and the different methods used to evaluate accuracy. Concerted efforts are needed to define a gold standard and quality metrics for real-world data.
Large-scale identification of novel transcriptional regulators of the aliphatic glucosinolate pathway in Arabidopsis
Authors: Chen Lin , Zeng Qi , Zhang Jiahao , Li Chao , Bai Xue , Sun Fengli , Kliebenstein Daniel J , Li Baohua
Published: September 2023

Aliphatic glucosinolates are a large group of plant secondary metabolites characteristic of Brassicaceae, including the model plant Arabidopsis. The diverse and complex degradation products of aliphatic glucosinolates contribute to plant responses to herbivory, pathogen attack, and environmental stresses. Most of the biosynthesis genes in the aliphatic glucosinolate pathway have been cloned in Arabidopsis, and the research focus has recently shifted to the regulatory mechanisms controlling aliphatic glucosinolate accumulation. Up till now, more than 40 transcriptional regulators have been identified as regulating the aliphatic glucosinolate pathway, but many more novel regulators likely remain to be discovered based on research evidence over the past decade. In the current study, we took a systemic approach to functionally test 155 candidate transcription factors in Arabidopsis identified by yeast one-hybrid assay, and successfully validated at least 30 novel regulators that could significantly influence the accumulation of aliphatic glucosinolates in our experimental set-up. We also showed that the regulators of the aliphatic glucosinolate pathway have balanced positive and negative effects, and glucosinolate metabolism and plant development can be coordinated. Our work is the largest scale effort so far to validate transcriptional regulators of a plant secondary metabolism pathway, and provides new insights into how the highly diverse plant secondary metabolism is regulated at the transcriptional level.
Narcissism Is Not Associated With Success in U.S. Army Soldier Training
Authors: Newman Jill C , Malek Angela M , Hibbeln Joseph R , Pregulman Marcie , Burbelo Gregory A , Turner Travis H , Marriott Bernadette P
Published: September 2023

Introduction

Narcissism has been studied for its role in leadership using various versions of the Narcissistic Personality Inventory (NPI). Narcissism is described as having a “dark and negative” side as well as a “positive or bright” side. The bright side of narcissism, in particular, has been studied for its role in leadership. In studies among military personnel in Finland and Hungary, the NPI has been associated with positive leadership traits. We assessed if measures of narcissistic personality were predictive of entrance to and graduation from the Army Ranger Course among United States (U.S.) Army personnel.

Materials and Methods

We included the NPI as one of the measures in the Ranger Resilience and Improved Performance on Phospholipid-bound Omega-3’s (RRIPP-3) study. RRIPP-3 was a double-blind, placebo-controlled dietary supplement intervention trial at Fort Benning, GA, that enrolled 555 officers when they entered the U.S. Army Infantry Basic Officer Leadership Course (IBOLC) with the intention to complete the U.S. Ranger School. RRIPP-3 volunteer participants consumed eight dietary supplements daily containing 2.3 g of omega-3 (krill oil) or macadamia nut oil (control) over a 20-week period. Blood spot samples were collected to monitor intake compliance. Cognitive functioning, resilience, and mood were assessed at approximately 14 and 16 weeks. Dietary intake was also assessed. The 40-item, forced-choice NPI was included to assess if three factors of narcissism: Leadership/Authority, Grandiose/Exhibitionism, and Entitlement/Exploitativeness measures of narcissistic personality were associated with entrance to and graduation from the Army Ranger Course.

Results

Of the 555 soldiers enrolled in RRIPP-3, there were no statistically significant differences in the total NPI scores comparing U.S. Army IBOLC officers who enrolled (n = 225) versus did not enroll (n = 330, p = .649) or graduated (n = 95; versus did not graduate [n = 460, p = .451]) from the Ranger Course. None of the three-factor NPI subscales differed statistically comparing either enrollment in (p = .442, .510, and .589, respectively) or graduation from the Ranger Course (p = .814, .508, and .813, respectively).

Conclusions

Although narcissism has been positively associated with military trainee success in other countries, we did not find an association between narcissism and trainee success among U.S. Army trainees, and accordingly the level of narcissism did not predict trainee success or failure.
Embracing Leadership: How Junior Medical Officers Shape the Future
Authors: Redondo Jose , Robbins Rachel
Published: September 2023

Transitioning from medical residency to an operational role challenges junior medical officers as their leadership skills are put to the test. In the multifaceted role of Military Medical Corps Officers, patient care remains paramount, and effective leadership hinges on core values. From clinical competence and mentorship to modeling behavior and fostering adaptability, this article underscores the importance of leadership development for junior officers as they transition from the training centers into the operational environment. Effective junior officer leaders become force multipliers, empowering their teams and cultivating future leaders to uphold the values essential to mission success.
Analysing mixed modes of the four solar-like oscillating subgiant stars
Authors: Çelik Orhan Z , Yıldız M , Örtel S
Published: September 2023

The observation of an unprecedented number of solar-like oscillating subgiant (SG) stars by the Kepler and TESS missions is crucial for the asteroseismic characterization of these stars, stellar population studies, and the study of stellar evolution theories. Owing to these missions, the fundamental parameters of the solar-like oscillating stars are precisely calculated from the evolution codes using the observed oscillation frequencies. Herein, we considered four solar-like oscillating SG stars. We obtained the fundamental parameters of the SG stars by constructing interior models using asteroseismic and non-asteroseismic observed parameters. The interior models of the four SG stars are constructed using the Modules for Experiments in Stellar Astrophysics code to effectively determine the fundamental properties. Using this method, the four solar-like oscillating SG stars are found to have masses and radii within the ranges of 1.16–1.75 M⊙ and 2.26–3.17 R⊙, respectively. The estimation accuracy of the typical asteroseismic radius, mass, and age is increased by fitting the observed and model reference frequencies. The typical uncertainties of the mass and radius are 3–4 ${{\ \rm per\ cent}}$ and 1–2 ${{\ \rm per\ cent}}$, respectively. Furthermore, the observed l = 1 frequencies, which showed a mixed mode for the first time, were also fitted to the models. Information regarding the gravity and density of the helium core was obtained by examining the mixed modes. Moreover, new asteroseismic methods for determining the age of SG stars are developed for the first time in this study.
Modelling variable linear polarization produced by Co-rotating Interaction Regions (CIRs) across optical recombination lines of Wolf–Rayet stars
Authors: Ignace R , Bjorkman J E , Chené A-N , Erba C , Fabiani L , Moffat A F J , Sincennes R , St-Louis N
Published: September 2023

Massive star winds are structured both stochastically (‘clumps’) and often coherently (Co-rotation Interaction Regions, or CIRs). Evidence for CIRs threading the winds of Wolf–Rayet (WR) stars arises from multiple diagnostics including linear polarimetry. Some observations indicate changes in polarization position angle across optical recombination emission lines from a WR star wind but limited to blueshifted Doppler velocities. We explore a model involving a spherical wind with a single conical CIR stemming from a rotating star as qualitative proof-of-concept. To obtain a realistic distribution of limb polarization and limb darkening across the pseudo-photosphere formed in the optically thick wind of a WR star, we used Monte Carlo radiative transfer (MCRT). Results are shown for a parameter study. For line properties similar to WR 6 (EZ CMa; HD 50896), combining the MCRT results, a simple model for the CIR, and the Sobolev approximation for the line formation, we were able to reproduce variations in both polarization amplitude and position angle commensurate with observations. Characterizing CIRs in WR winds has added importance for providing stellar rotation periods since the vsin i values are unobtainable because the pseudo-photosphere forms in the wind itself.
Epigenetic reprogramming of a distal developmental enhancer cluster drivesSOX2overexpression in breast and lung adenocarcinoma
Authors: Abatti Luis E , Lado-Fernández Patricia , Huynh Linh , Collado Manuel , Hoffman Michael M , Mitchell Jennifer A
Published: September 2023

Enhancer reprogramming has been proposed as a key source of transcriptional dysregulation during tumorigenesis, but the molecular mechanisms underlying this process remain unclear. Here, we identify an enhancer cluster required for normal development that is aberrantly activated in breast and lung adenocarcinoma. Deletion of the SRR124–134 cluster disrupts expression of the SOX2 oncogene, dysregulates genome-wide transcription and chromatin accessibility and reduces the ability of cancer cells to form colonies in vitro. Analysis of primary tumors reveals a correlation between chromatin accessibility at this cluster and SOX2 overexpression in breast and lung cancer patients. We demonstrate that FOXA1 is an activator and NFIB is a repressor of SRR124–134 activity and SOX2 transcription in cancer cells, revealing a co-opting of the regulatory mechanisms involved in early development. Notably, we show that the conserved SRR124 and SRR134 regions are essential during mouse development, where homozygous deletion results in the lethal failure of esophageal–tracheal separation. These findings provide insights into how developmental enhancers can be reprogrammed during tumorigenesis and underscore the importance of understanding enhancer dynamics during development and disease.
Quantum biological insights into CRISPR-Cas9 sgRNA efficiency from explainable-AI driven feature engineering
Authors: Noshay Jaclyn M , Walker Tyler , Alexander William G , Klingeman Dawn M , Romero Jonathon , Walker Angelica M , Prates Erica , Eckert Carrie , Irle Stephan , Kainer David , Jacobson Daniel A
Published: September 2023

CRISPR-Cas9 tools have transformed genetic manipulation capabilities in the laboratory. Empirical rules-of-thumb have been developed for only a narrow range of model organisms, and mechanistic underpinnings for sgRNA efficiency remain poorly understood. This work establishes a novel feature set and new public resource, produced with quantum chemical tensors, for interpreting and predicting sgRNA efficiency. Feature engineering for sgRNA efficiency is performed using an explainable-artificial intelligence model: iterative Random Forest (iRF). By encoding quantitative attributes of position-specific sequences for Escherichia coli sgRNAs, we identify important traits for sgRNA design in bacterial species. Additionally, we show that expanding positional encoding to quantum descriptors of base-pair, dimer, trimer, and tetramer sequences captures intricate interactions in local and neighboring nucleotides of the target DNA. These features highlight variation in CRISPR-Cas9 sgRNA dynamics between E. coli and H. sapiens genomes. These novel encodings of sgRNAs enhance our understanding of the elaborate quantum biological processes involved in CRISPR-Cas9 machinery.
Comprehensive and realistic simulation of tumour genomic sequencing data
Authors: O’Sullivan Brian , Seoighe Cathal
Published: September 2023

Accurate identification of somatic mutations and allele frequencies in cancer has critical research and clinical applications. Several computational tools have been developed for this purpose but, in the absence of comprehensive ‘ground truth’ data, assessing the accuracy of these methods is challenging. We created a computational framework to simulate tumour and matched normal sequencing data for which the source of all loci that contain non-reference bases is known, based on a phased, personalized genome. Unlike existing methods, we account for sampling errors inherent in the sequencing process. Using this framework, we assess accuracy and biases in inferred mutations and their frequencies in an established somatic mutation calling pipeline. We demonstrate bias in existing methods of mutant allele frequency estimation and show, for the first time, the observed mutation frequency spectrum corresponding to a theoretical model of tumour evolution. We highlight the impact of quality filters on detection sensitivity of clinically actionable variants and provide definitive assessment of false positive and false negative mutation calls. Our simulation framework provides an improved means to assess the accuracy of somatic mutation calling pipelines and a detailed picture of the effects of technical parameters and experimental factors on somatic mutation calling in cancer samples.
Most protein domains exist as variants with distinct functions across cells, tissues and diseases
Authors: Vitting-Seerup Kristoffer
Published: September 2023

Protein domains are the active subunits that provide proteins with specific functions through precise three-dimensional structures. Such domains facilitate most protein functions, including molecular interactions and signal transduction. Currently, these protein domains are described and analyzed as invariable molecular building blocks with fixed functions. Here, I show that most human protein domains exist as multiple distinct variants termed ‘domain isotypes’. Domain isotypes are used in a cell, tissue and disease-specific manner and have surprisingly different 3D structures. Accordingly, domain isotypes, compared to each other, modulate or abolish the functionality of protein domains. These results challenge the current view of protein domains as invariable building blocks and have significant implications for both wet- and dry-lab workflows. The extensive use of protein domain isotypes within protein isoforms adds to the literature indicating we need to transition to an isoform-centric research paradigm.
Racism hurts, can antiracism heal?: Positive mental health correlates of antiracist engagement
Authors: Brannon Tiffany N
Published: September 2023

Racism can hurt by negatively impacting mental health. For instance, large-scale events tied to racism like the May 2020 police-involved murder of George Floyd have been linked to poor mental health indicators (e.g. depression and anxiety). Notably, racism can spark antiracist engagement—support for addressing systemic racism. For example, Floyd's murder sparked unprecedented antiracist engagement, including heightened Black Lives Matter (BLM) support and protest participation. The present research explored the potential that antiracist engagement can heal: be positively associated with well-being. First, study 1 found that state-level BLM engagement (i.e. protest numbers, antiracism information-seeking on Google/YouTube) during an 8-week period following Floyd's death was associated with positive mental health indicators (i.e. lower depression and anxiety, higher self-rated health). It found these effects among racial/ethnic minorities (e.g. Black/African Americans, Hispanics, N = 161,359) and Whites (N = 516,002). Then, study 2 examined social media data (i.e. tweets) and emotional well-being. It used a measure of happiness indexed across 144,649,285,571 tweets from 2019 through 2021. It found a positive correlation between the volume of tweets with antiracist engagement content (e.g. referenced efforts to address systemic racism) and the happiness measure. Finally, study 3 examined antiracism protest data/information-seeking and a sample of BLM tweets (N = 100,321) posted between April and July 2020. Conceptually replicating studies 1–2, study 3 found that antiracist engagement was associated with greater positive emotion/sentiment (e.g. happiness) relative to negative emotion/sentiment (e.g. anxiety). Relevant to theory and policy, the observed results suggest that antiracist engagement can be associated with benefits for well-being across racial/ethnic groups.
The unique 3D arrangement of macrophage galactose lectin enables Escherichia coli lipopolysaccharide recognition through two distinct interfaces
Authors: Abbas Massilia , Maalej Meriem , Nieto-Fabregat Ferran , Thépaut Michel , Kleman Jean-Philippe , Ayala Isabel , Molinaro Antonio , Simorre Jean-Pierre , Marchetti Roberta , Fieschi Franck , Laguri Cedric
Published: September 2023

Lipopolysaccharides are a hallmark of gram-negative bacteria, and their presence at the cell surface is key for bacterial integrity. As surface-exposed components, they are recognized by immunity C-type lectin receptors present on antigen-presenting cells. Human macrophage galactose lectin binds Escherichia coli surface that presents a specific glycan motif. Nevertheless, this high-affinity interaction occurs regardless of the integrity of its canonical calcium-dependent glycan-binding site. NMR of macrophage galactose-type lectin (MGL) carbohydrate recognition domain and complete extracellular domain revealed a glycan-binding site opposite to the canonical site. A model of trimeric macrophage galactose lectin was determined based on a combination of small-angle X-ray scattering and AlphaFold. A disulfide bond positions the carbohydrate recognition domain perpendicular to the coiled-coil domain. This unique configuration for a C-type lectin orients the six glycan sites of MGL in an ideal position to bind lipopolysaccharides at the bacterial surface with high avidity.
Representing the special linear group with block unitriangular matrices
Authors: Urschel John
Published: September 2023

We prove that every element of the special linear group can be represented as the product of at most six block unitriangular matrices, and that there exist matrices for which six products are necessary, independent of indexing. We present an analogous result for the general linear group. These results serve as general statements regarding the representational power of alternating linear updates. The factorizations and lower bounds of this work immediately imply tight estimates on the expressive power of linear affine coupling blocks in machine learning.
Macroprudential Policy, Mortgage Cycles, and Distributional Effects: Evidence from the United Kingdom
Authors: Peydró José-Luis , Rodriguez-Tous Francesc , Tripathy Jagdish , Uluc Arzu
Published: September 2023

We analyze the distributional effects of macroprudential policy on mortgage cycles by exploiting the U.K. mortgage register and a 2014 15% limit imposed on lenders’ high loan-to-income (LTI) mortgages. Constrained lenders issue fewer and more expensive high-LTI mortgages, with stronger effects on low-income borrowers. Unconstrained lenders strongly substitute high-LTI loans in local areas with higher constrained lender presence, but not high-LTI loans to low-income borrowers—consistent with adverse selection problems—implying lower overall credit to low-income borrowers. Consistently, policy-affected areas experience lower house price growth postregulation and, following the Brexit referendum (negative aggregate shock), better house price growth and lower mortgage defaults for low-income borrowers.
Reproductive health in female patients with systemic sclerosis: a cross-sectional study
Authors: Dai Liyi , Xu Dan , Li Xinyi , Huang Sicheng , Duan Xiangyue , Zheng Ai , Yang Jing , Zhao Jie , Zeng Lin , Mu Rong
Published: September 2023

Objectives

To explore the status of reproductive health and related factors in female patients with systemic sclerosis (SSc).

Methods

A cross-sectional study was conducted among female patients from the Chinese Organization for Scleroderma through a questionnaire. Data on the status of reproductive health including fertility condition and menstrual status were obtained. The clinical and laboratory data of SSc were collected. For patients with pregnancies after disease onset, each pregnancy was matched with a healthy control. Associations between clinical characteristics and the status of reproductive health were analysed.

Results

A total of 342 female patients with SSc were included, and 31.8% (108/342, 95% CI 26.9%–36.7%) of them presented problems with reproductive health. Compared with the national data, the menopausal age of patients with disease onset before menopause was earlier (45.2 ± 6.1 vs 48.2 ± 4.4, P < 0.001). Age of disease onset (P = 0.018) and digital ulcer (P = 0.020) had statistically significant effects on menopausal age. Although the infertility rate of patients was not increased, the rate of spontaneous abortions was higher compared with the national data (9/74, 12.2% vs 4.3%, P < 0.001). Compared with the healthy control group, the rate of premature infants (12/55, 21.8% vs 7/110, 6.4%, P = 0.003), low birth weight infants (15/55, 27.3% vs 6/110, 5.5%, P < 0.001), and cesarean section (27/55, 49.1% vs 21/110, 19.1%, P < 0.001) increased significantly.

Conclusion

The impairment of reproductive health is common and in many quarters in patients with SSc. Further action should be taken to improve reproductive health in patients with SSc, especially in maternal care.