bluuebunny/crossref_metadata_2025 huggingface dataset:
Hazard of Failed Nonoperative Management for Symptomatic Accessory Navicular in Children and Adolescents: A Population-Based Case-Cohort Study
Authors: Nguyen Hillary Brenda , Miller Patricia , Mahan Susan , Spencer Samantha , Micheli Lyle , Kasser James , May Collin
Published: June 2024

Background:

The accessory navicular (AN) is an idiopathic condition of the foot present in 4% to 21% of the population. Most ANs remain asymptomatic, but children and adolescents who develop symptoms can have remarkably reduced quality of life. Although many respond to conservative measures, surgery is occasionally needed. Our purpose was to determine factors associated with the failure of nonoperative management.

Methods:

This single-institution retrospective case-cohort study included patients up to age 19 years presenting between 2000 and 2021 with symptomatic AN and treated with standard-of-care. All 298 surgical cases, indicating failed nonoperative treatment, were included. For the subcohort, 299 patients were randomly sampled from all eligible patients, regardless of treatment. Baseline characteristics were summarized for the surgical cases and subcohort. Proportional hazards assumptions were checked and stratification implemented when necessary. Marginal structural proportional hazard modeling was used to estimate hazard ratios with 95% confidence intervals via inverse probability and LinYing weighting methods.

Results:

The 298 surgical cases failed nonoperative management at a median of 5.2 months (IQR, 2.0–11.6 mo). In the subcohort, 86 failures of nonoperative management and 213 nonfailures constituted a 28.8% surgery rate. In both cohorts, nearly all patients played sports. Univariate proportional hazard modeling found older age (P=0.02) and activity limitation (P<0.001) at presentation, female sex (P=0.002), higher BMI (P=0.01), AN on the right (P<0.001), and bone marrow edema of the AN (P<0.001) and navicular body (P<0.001) on MRI were associated with increased hazard of nonoperative failure. Nearly all of the surgical cohort reported improvement in pain (278/296, 94%) and returned to their primary sport (236/253, 93%) after surgery. Most also experienced full resolution of symptoms (187/281, 67%).

Conclusions:

Symptomatic AN predominantly affects female athletes, leading to surgery in 28.8% of our subcohort. Conservative treatment may be less successful—and therefore surgery could be more strongly considered—in older age, activity limitation at presentation, female sex, higher BMI, right-sided AN, and bone marrow edema on MRI. Surgery is effective for symptomatic and functional improvement.

Level of Evidence:

Case-cohort—Level III.
Comparing Gender Congruency in Nonsurgical versus Postsurgical Top Surgery Patients: A Prospective Survey Study
Authors: Shue Shirley , Joo Alex , Xu Jing , Gu Garrick , Camargo Anthony , Bronson Isaac , Lister Rachel , Hawley Nathan , Morrison Daniel Alexander , McIntyre Joyce K.
Published: June 2024

Background:

Gender dysphoria can result in reduced quality of life. Treatments include hormone replacement therapy (HRT) and gender-affirming surgery. Our study compared congruency, satisfaction, and discrimination in patients who underwent top surgery and HRT versus HRT alone. We hypothesized improved outcomes in top surgery patients but that lack of access is a common barrier.

Methods:

Transgender and nonbinary subjects who underwent at least 6 months of HRT were recruited and answered questions on gender congruency, discrimination, and barriers to care. Surgical patients were asked about postoperative satisfaction using the BREAST-Q. A Mann-Whitney test compared survey responses between study arms.

Results:

One hundred twelve eligible subjects completed the survey. Surgical subjects answered significantly more positively (P < 0.001) on all questions regarding gender congruency. The greatest difference was observed in how subjects’ physical bodies represented their gender identity, where the surgery group rated higher on the five-point Likert scale by 2.0 points (P < 0.001). Surgical patients also reported less violence, verbal abuse, and discrimination (P < 0.003). Within the hormone arm, 87.1% stated desire for surgery and 62.5% declared barriers to surgery, with cost and insurance coverage representing the most common barriers. Finally, surgical subjects reported high satisfaction on the BREAST-Q, scoring more than 3.0 in all categories of breast augmentation and more than 2.6 for breast reduction on a four-point Likert scale.

Conclusions:

Top surgery, in addition to HRT, significantly improves gender congruency and decreases discrimination and abuse, compared with HRT alone. Unfortunately, barriers including cost and lack of insurance continue to be obstacles for care.
Liver disease and transplantation in telomere biology disorders: An international multicenter cohort
Authors: Wang YunZu Michele , Kaj-Carbaidwala Batul , Lane Adam , Agarwal Suneet , Beier Fabian , Bertuch Alison , Borovsky Kristin A. , Brennan Steven K. , Calado Rodrigo T. , Catto Luiz Fernando B. , Dufour Carlo , Ebens Christen L. , Fioredda Francesca , Giri Neelam , Gloude Nicholas , Goldman Frederick , Hertel Paula M. , Himes Ryan , Keel Sioban B. , Koura Divya T. , Kratz Christian P. , Kulkarni Sakil , Liou Iris , Nakano Taizo A. , Nastasio Silvia , Niewisch Marena R. , Penrice Daniel D. , Sasa Ghadir S. , Savage Sharon A. , Simonetto Douglas A. , Ziegler David S. , Miethke Alexander G. , Myers Kasiani C. ,   on behalf of the Clinical Care Consortium for Telomere-associated Ailments (CCCTAA)
Published: June 2024

Background:

Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes.

Methods:

Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study.

Results:

Group A (“Advanced”) included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M (“Mild”) included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6–13.2 y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant.

Conclusions:

LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.
AMPED study: Protocol for a randomized controlled trial of different doses of aerobic exercise training
Authors: Stine Jonathan G. , Hummer Breianna , Smith Nataliya , Tressler Heather , Heinle J. Westley , VanKirk Kyra , Harris Sara , Moeller Matthew , Luzier Gavin , DiJoseph Kara , Hussaini Zeba , Jackson Ryan , Rodgers Brandon , Schreibman Ian , Stonesifer Elizabeth , Tondt Justin , Sica Chris , Nighot Prashant , Chinchilli Vernon M. , Loomba Rohit , Sciamanna Christopher , Schmitz Kathryn H. , Kimball Scot R.
Published: June 2024

Recently renamed, metabolic dysfunction–associated steatotic liver disease remains a leading cause of chronic liver disease worldwide. Regular physical activity is recommended as a treatment for all with this condition because it is highly efficacious, especially when exercise training is undertaken with a specific goal in mind. Despite decades of research demonstrating exercise’s efficacy, key questions remain about the mechanism of benefit and most efficacious dose, as well as the independent impact on liver histology. To answer these questions, we present the design of a 16-week randomized controlled clinical trial of 45 adults aged 18–69 years with metabolic dysfunction–associated steatohepatitis. The primary aim of this study is to better understand the dose required and mechanisms to explain how exercise impacts multiple clinical end points in metabolic dysfunction–associated steatohepatitis. The primary outcome is MRI-measured liver fat. Secondary outcomes include other biomarkers of liver fibroinflammation, liver histology, and mechanistic pathways, as well as cardiometabolic risk and quality of life. This is the first study to compare different doses of exercise training to determine if there is a differential impact on imaging and serum biomarkers as well as liver histology.
Blood pressure measurement and assessment of arterial structure and function: an expert group position paper
Authors: Asmar Roland , Stergiou George , de la Sierra Alejandro , Jelaković Bojan , Millasseau Sandrine , Topouchian Jirar , Shirai Kohji , Blacher Jacques , Avolio Alberto , Jankowski Piotr , Parati Gianfranco , Bilo Grzegorz , Rewiuk Krzysztof , Mintale Iveta , Rajzer Marek , Agabiti-Rosei Enrico , Ince Can , Postadzhiyan Arman , Zimlichman Reuven , Struijker-Boudier Harry , Benetos Athanase , Bäck Magnus , Tasic Nebojsa , Sirenko Yuriy , Zelveian Parounak , Wang Hongyu , Fantin Francesco , Kotovskaya Yulia , Ezhov Marat , Kotsis Vasilios
Published: June 2024

Measuring blood pressure (BP) and investigating arterial hemodynamics are essential in understanding cardiovascular disease and assessing cardiovascular risk. Several methods are used to measure BP in the doctor's office, at home, or over 24 h under ambulatory conditions. Similarly, several noninvasive methods have been introduced for assessing arterial structure and function; these methods differ for the large arteries, the small ones, and the capillaries. Consequently, when studying arterial hemodynamics, the clinician is faced with a multitude of assessment methods whose technical details, advantages, and limitations are sometimes unclear. Moreover, the conditions and procedures for their optimal implementation, and/or the reference normality values for the parameters they yield are not always taken into sufficient consideration. Therefore, a practice guideline summarizing the main methods and their use in clinical practice is needed.

This expert group position paper was developed by an international group of scientists after a two-day meeting during which each of the most used methods and techniques for blood pressure measurement and arterial function and structure evaluation were presented and discussed, focusing on their advantages, limitations, indications, normal values, and their pragmatic clinical application.
Humor Styles in Healthcare Professionals
Authors: Leñero-Cirujano Miriam , Moro-Tejedor Mª Nieves , Torres-González Juan Ignacio , González-Ordi Héctor , Gómez-Higuera Jacinto
Published: June 2024

Using humor as a caregiving strategy can help professionals perceive daily and work-related events from a more optimistic and light-hearted perspective. The main objective of this study was to analyze humor styles among health care professionals. A cross-sectional and correlational design was employed. Data were collected using the Humor Styles Questionnaire, which measures four humor styles: affiliative, self-enhancing, aggressive, and self-defeating humor. Health care professionals scored higher in positive humor than negative humor. Age exhibited a negative correlation with positive humor. Significant differences were observed between marital status and affiliative and self-enhancing humor, professional category and hospital unit with aggressive humor, shift work and self-enhancing humor, and type of contract and experience with affiliative humor. Health care professionals employ various humor styles based on their social and work contexts. It is crucial for health care professionals to receive training in the use of positive humor to consciously avoid humor styles that can hinder well-being.
Effects of Qigong Therapy on the Psychological Well-Being, Physical Health State, Sleep State, and Life Satisfaction of Older Adults Living in Community
Authors: Lee Donghee , Gu Minkyung , Sok Sohyune
Published: June 2024

Older adults living in a community are looking for alternative and complementary methods to improve their healthy longevity and quality of life. This study aimed to examine the effects of the Qigong therapy on psychological well-being, physical health state, sleep state, and life satisfaction of older adults living in community. This study used a quasi-experimental pretest-posttest control group design. The study samples were 69 older adults (intervention, n = 34; control, n = 35) over 65 years old in community in South Korea. Qigong therapy was performed 50 minutes per session, twice a week for a total of 20 times over a 10-week period in a comfortable and quiet environment without external noise. Measures were the study participant’s general characteristics survey, psychological well-being scale, Cornell Medical Index—Korean version, sleep scale, and life satisfaction scale standardized for the elderly. Effects of Qigong therapy according to interaction effect over time and the group showed statistically significant differences in psychological well-being, physical health state, sleep state, and life satisfaction. This study suggests that Qigong therapy was an effective nursing intervention for improving the psychological well-being, physical health state, sleep state, and life satisfaction of older adults living in community.
Clinical Characteristics and Prognosis of Older Adult Patients With Necrotizing Pancreatitis: A single center retrospective study
Authors: Wu Yue , Lu JiongDi , Cao Feng , Li Fei
Published: June 2024

Background:

Acute pancreatitis (AP) is a common condition encountered during clinical practice; 20% of patients have pancreatic necrosis, and the mortality is high. This study aimed to explore the clinical characteristics and prognosis of older adult patients with necrotizing pancreatitis (NP).

Methods:

We searched for 1159 patients with AP admitted to the General Surgery Department of Xuanwu Hospital from January 2014 to December 2021. After screening medical history and imaging examinations, a total of 109 patients were divided into a death group (n=31) and a survival group (n=78), and their clinical characteristics and prognosis were further analyzed.

Results:

In the death group, the scope of pancreatic necrosis was more extensive, the evidence of infection was apparent, the nutritional status and the clinical outcome were worse; In addition, patients in the death group have a higher proportion of organ failure and infection, and longer intensive care unit (ICU) hospitalization time.

Conclusion:

Preoperative persistent organ failure (POF) and prolonged hospitalization in ICU are independent risk factors leading to increased mortality in elderly patients with NP. Early identification of risk factors ,timely drug treatment and surgical intervention are essential to improve the prognosis of older adult patients and reduce mortality.
Epidemiology of Hamstring Tears in National Collegiate Athletic Association Athletes: Findings From the National Collegiate Athletic Association Injury Surveillance Program Between 2014/2015 and 2018/2019
Authors: Boltz Adrian J. , Hooper Nicholas , Satalich James , Cheatham Seth , O'Connell Robert , Rao Neel , Garcia Reagan E. , Collins Christy L. , Chandran Avinash
Published: June 2024

Objective:

To describe the epidemiology of hamstring tears in National Collegiate Athletic Association (NCAA) sports.

Design:

Descriptive epidemiology study. Athletic trainers from NCAA schools reported injuries to the NCAA Injury Surveillance Program.

Setting:

A convenience sample of NCAA hamstring tear injuries during the 2014/2015 through 2018/2019 academic years.

Patients (or Participants):

NCAA student-athletes.

Independent Variables:

Sport, sex, event type, season segment, injury history, and activity at the time of injury.

Main Outcome Measures:

Injury counts, rates, and proportions were used.

Results:

Two thousand ninety-six hamstring tears from 8 474 400 athlete-exposures (AEs) were reported (2.47 per 10 000 AEs). Rates were highest in Men's Soccer (5.97 per 10 000 AEs) and Women's Soccer (3.13 per 10 000 AEs), among all Men's and Women's sports, respectively. Competition-related rates in Men's and Women's sports were highest in 2015 to 2016 then followed a decreasing pattern across the remainder of the study period. Among sex-comparable sports, rates were higher in men's (compared with women's) Baseball/Softball, Soccer, and Track and Field. The prevalence of recurrent injuries was comparable among men's (14.8%) and women's (11.5%) sports. Time loss hamstring tears were more prevalent in Men's sports than Women's sports [injury proportion ratio = 1.33; 95% confidence interval, (1.21, 1.47)].

Conclusions:

Overall, hamstring tear rates were higher across all Men's sports compared with Women's sports. Rates across event type were comparable in several sports; and so, adjustments to practice are needed considering that practice environments are more modifiable than competitions. Indeed, improving hamstring tear prevention programs to reduce the burden of this injury in NCAA athletes remains critical.
Music to Define a Generation: Factors Associated With Hearing Protection Use at Music Venues
Authors: Lin Matthew E. , Long Ryan , Iyer Avinash , Ayo-Ajibola Oluwatobiloba , Choi Janet S. , Doherty Joni K.
Published: June 2024

Objectives

Excessive noise levels in music venues can negatively impact long-term hearing health. We investigated the prevalence, characteristics, and factors associated with hearing protection use among music event attendees.

Study Design

Cross-sectional cohort.

Methods

Adult participants (2,352) from online music forums completed a questionnaire assessing attendance at music events, hearing protection (HP) usage, type, and frequency, along with history of hearing-related symptoms and medical history. Primary outcome was defined as HP use at music venues. Data were characterized using descriptive statistics, paired t tests, and Pearson's chi-squared tests. Multivariable regression analysis elicited factors associated with any and regular HP use.

Results

Our 2,352 respondents were primarily male (61.3%) and on average 28.7 years old (SD = 7.0). Of the respondents, 60.6% reported using HP, and 33.2% reported regular use; high-fidelity earplugs were the most used HP type (57.5%). HP use was associated with significantly fewer reports of negative hearing-related symptoms. In a multivariable regression model, factors associated with less likelihood of HP use included being female (vs male, OR = 0.74, CI = [0.55–0.98]), less concern about effects on hearing (OR = 0.53, CI = [0.45–0.61]), and pop music event attendance (vs EDM, OR = 0.40, CI = [0.22–0.72]). Increased attendance frequency in the past year was associated with higher likelihood of regular HP use (OR = 1.07, CI = [1.04–1.09]). Decreased attendance duration was associated with decreased likelihood (OR = 0.09, CI = [0.03–0.33]).

Conclusion

HP use prevalence was high, while frequent use remained low. HP use was significantly associated with reduced hearing-related symptoms. Demographic factors, otologic symp-tomology, and attendance-related characteristics were associated with HP use. These findings may guide interventions to increase adoption at music venues.

Level of Evidence

4
Three-dimensional printing technology applied to the production of prosthesis: A systemic narrative review
Authors: Choo Yoo Jin , Kim Jang Hwan , Chang Min Cheol
Published: June 2024

The purpose of this scoping review was to investigate the effects of 3-dimensional (3D)-printed prostheses. Articles published up to August 19, 2023, were searched in the PubMed, Cochrane Library, Embase, and Scopus databases. The search terms used were “3D printed prosthesis,” “3D printed prostheses,” “3D printed prosthe*,” “3D printed artificial arm,” “3D printed artificial leg,” “3D printing prosthesis,” “3D printing prostheses,” “3D printing prosthe*,” “3D printing artificial arm,” and “3D printing artificial leg.” This review included studies that applied 3D-printed prostheses to upper- or lower-limb amputees. Case reports, conference abstracts, presentations, reviews, and unidentified articles were excluded from the analysis. A total of 937 articles were identified, 11 of which were included after confirming eligibility through the title, abstract, and full text. The results indicated that the 3D-printed prostheses demonstrated the ability to substitute for the functions of impaired limbs, similar to conventional prostheses. Notably, the production cost and weight were reduced compared with those of conventional prostheses, increasing patient satisfaction. The use of 3D-printed prostheses is expected to gain prominence in future clinical practice. However, concerns regarding the durability of 3D-printed prostheses have increased among users. Therefore, there is an ongoing need to explore highly durable materials that can withstand the weight of the user without breaking easily. In addition, advancements are required in technologies that enable the depiction of various skin tones and the production of smaller-sized prostheses suitable for clothing.
Adaptation of a fluoroquinolone-sensitive
Shigella sonnei
to norfloxacin exposure
Authors: Wong Bao Chi , Law Soffi Kei Kei , Md Zoqratt Muhammad Zarul Hanifah , Ayub Qasim , Tan Hock Siew
Published: June 2024

Shigella
causes shigellosis that requires antibiotic treatment in severe cases. Sublethal antibiotic concentrations can promote resistance, but their effect on antibiotic-sensitive bacteria before resistance development is unclear. This study investigated the effects of sublethal norfloxacin (NOR) challenges on a NOR-sensitive strain,
Shigella sonnei
UKMCC1015. Firstly, the whole genome of
S. sonnei
UKMCC1015 was assembled, and 45 antimicrobial resistance (AMR) genes were identified. Interestingly, transcriptomic analysis showed that low NOR levels do not change either the expression of the AMR genes or NOR targets such as
gyrA
. Instead, multiple ribosomal protein genes were downregulated, which could be attributed to decreased ribosomal protein promoter activity, modulated by elevated guanosine pentaphosphate and tetraphosphate (ppGpp) levels. This alarmone is involved in the bacterial stringent response during environmental stress, and it is mainly produced from the ppGpp synthetase (
relA
). Additionally, we observed that a
relA
overexpression (prolonged period of elevated ppGpp levels) may negatively affect the NOR tolerance of the bacteria. In conclusion, this study revealed that a NOR-sensitive strain responds differently to sublethal NOR than commonly reported in resistant strains.
Effective T-matrix of a cylinder filled with a random two-dimensional particulate
Authors: Napal K. K. , Piva P. S. , Gower A. L.
Published: June 2024

When a wave, such as sound or light, scatters within a densely packed particulate, it can be rescattered many times between the particles, which is called multiple scattering. Multiple scattering can be unavoidable when trying to use sound waves to measure a dense particulate, such as a composite with reinforcing fibres. Here, we solve from first principles multiple scattering of scalar waves, including acoustic, for any frequency from a set of two-dimensional particles confined in a circular area. This case has not been solved yet, and its solution is important to perform numerical validation, as particles within a cylinder require only a finite number of particles to perform direct numerical simulations. The method we use involves ensemble averaging over particle configurations, which leads us to deduce an effective T-matrix for the whole cylinder, which can be used to easily describe the scattering from any incident wave. In the specific case when the particles are monopole scatterers, the expression of this effective T-matrix simplifies and reduces to the T-matrix of a homogeneous cylinder with an effective wavenumber

k
⋆

. To validate our theoretical predictions, we develop an efficient Monte Carlo method and conclude that our theoretical predictions are highly accurate for a broad range of frequencies.
Multi-ancestry Genome-Wide Association Meta-Analysis Identifies Novel Loci in Atopic Dermatitis
Authors: Oliva Meritxell , Sarkar Mrinal K. , March Michael E. , Saeidian Amir Hossein , Mentch Frank D. , Hsieh Chen-Lin , Tang Fanying , Uppala Ranjitha , Patrick Matthew T. , Li Qinmengge , Bogle Rachael , Kahlenberg J. Michelle , Watson Deborah , Glessner Joseph T. , Tsoi Lam C. , Hakonarson Hakon , Gudjonsson Johann E. , Smith Kathleen M. , Riley-Gillis Bridget
Published: June 2024

Atopic dermatitis (AD) is a highly heritable and common inflammatory skin condition affecting children and adults worldwide. Multi-ancestry approaches to AD genetic association studies are poised to boost power to detect genetic signal and identify ancestry-specific loci contributing to AD risk. Here, we present a multi-ancestry GWAS meta-analysis of twelve AD cohorts from five ancestral populations totaling 56,146 cases and 602,280 controls. We report 101 genomic loci associated with AD, including 15 loci that have not been previously associated with AD or eczema. Fine-mapping, QTL colocalization, and cell-type enrichment analyses identified genes and cell types implicated in AD pathophysiology. Functional analyses in keratinocytes provide evidence for genes that could play a role in AD through epidermal barrier function. Our study provides new insights into the etiology of AD by harnessing multiple genetic and functional approaches to unveil the mechanisms by which AD-associated variants impact genes and cell types.

Disclosure Statement

BRG, MO, CH, KMS are employees of AbbVie. FT was an employee of AbbVie at the time of the study. JEG (University of Michigan) has received research support from AbbVie, Janssen, Almirall, Prometheus Biosciences/Merck, BMS/Celgene, Boehringer Ingelheim, Galderma, Eli Lilly, and advisor to Sanofi, Eli Lilly, Galderma, BMS, Boehringer Ingelheim. MKS, RU, MTP, QL, RW, JMK, LCT are employees of University of Michigan and have no funding to disclose. MEM, AHS, FDM, DW, JTG, HH are employees of the Children’s Hospital of Philadelphia and no funding to disclose. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.
Genotype by environment interactions in gene regulation underlie the response to soil drying in the model grassBrachypodium distachyon
Authors: Yun Jie , Burnett Angela C. , Rogers Alistair , Des Marais David L.
Published: June 2024

Gene expression is a quantitative trait under the control of genetic and environmental factors and their interaction, so-called GxE. Understanding the mechanisms driving GxE is fundamental for ensuring stable crop performance across environments and for predicting the response of natural populations to climate change. Gene expression is regulated through complex molecular networks, yet the interactions between genotype and environment on genome-wide regulatory networks are rarely considered. In this study, we model genome-scale gene expression variation between two natural accessions of the model grassBrachypodium distachyonand their response to soil drying. We identified genotypic, environmental, and GxE responses in physiological, metabolic, and gene expression traits. We then identified gene regulation conservation and variation among conditions and genotypes, simplified as co-expression clusters in each combination of genotype and environmental treatment. Putative gene regulatory interactions are inferred as network edges with a graphical modelling approach, resulting in hypotheses about gene-gene interactions specific to -- or with higher affinity in -- one genotype, one treatment, or in one genotype under treatment. We further find that some gene-gene interactions are conserved across conditions such that differential expression of one gene is apparently transmitted to a target gene. These variably detected edges cluster together in co-expression modules, suggestive of different constraints or selection strength acting on specific pathways. These variable features of gene regulatory networks may represent candidates modulate environmental response via genome editing, and suggest possible targets of evolutionary change in gene regulatory networks associated with phenotypic plasticity.
Manipulation of Photosensory and Circadian Signalling Restricts Developmental Plasticity in Arabidopsis
Authors: Battle Martin William , Ewing Scott Fraser , Dickson Cathryn , Obaje Joseph , Edgeworth Kristen N. , Bindbeutel Rebecca , Antoniou Kourounioti Rea , Nusinow Dmitri A. , Jones Matthew Alan
Published: June 2024

Abstract

Plants exploit developmental plasticity to adapt their growth and development to prevailing environmental cues. This developmental plasticity provides a selective and competitive advantage in nature but is obstructive during large-scale, intensive agricultural practices since economically important traits (including vegetative growth and flowering time) can widely vary depending on local environmental conditions. This prevents accurate prediction of harvesting times and produces a variable crop. We sought to restrict developmental plasticity by manipulating signalling systems that govern plants’ responses to environmental signals. Mathematical modelling of plant growth and development predicted a reduction in plant responses to changing environments when circadian and light signaling pathways were manipulated. We tested this hypothesis by utilising a constitutively-active allele of the plant photoreceptor phytochromeB, along with disruption of the circadian system via mutation ofEARLY FLOWERING3.We found that the combination of these manipulations produced plants that are less responsive to light and temperature cues. These engineered plants have uniform vegetative growth and flowering time and demonstrate how developmental plasticity can be limited whilst maintaining plant productivity. This has significant implications for future agriculture in both open fields and controlled environments.
The genome of the cryopelagic Antarctic bald notothen,Trematomus borchgrevinki
Authors: Rayamajhi Niraj , Rivera-Colón Angel G. , Minhas Bushra Fazal , Cheng C.-H. Christina , Catchen Julian M.
Published: June 2024

The Antarctic bald notothen,Trematomus borchgrevinki(Notothenioidae) occupies a high latitude, ice-laden environment and represents an extreme example of cold-specialization among fishes. We present the first, high quality, long-read genome of a femaleT. borchgrevinkiindividual comprised of 23 putative chromosomes, the largest of which is 65 megabasepairs (Mbp) in length. The total length of the genome 935.13 Mbp, composed of 2,095 scaffolds, with a scaffold N50 of 42.80 Mbp. Annotation yielded 22,567 protein coding genes while 54.75% of the genome was occupied by repetitive elements; an analysis of repeats demonstrated that an expansion occurred in recent time. Conserved synteny analysis revealed that the genome architecture ofT. borchgrevinkiis largely maintained with other members of the notothenioid clade, although several significant translocations and inversions are present, including the fusion of orthologous chromosomes 8 and 11 into a single element. This genome will serve as a cold-specialized model for comparisons to other members of the notothenioid adaptive radiation.
The potential applications of high-resolution 3D scanners in the taxonomic classification of insects
Authors: Peacock Cameron J , Romeu-Evans William , Hassall Christopher , Goodman Simon
Published: June 2024

The phenotypic classification of small biological specimens, such as insects, can be dependent on phenotypic features that are difficult to observe and communicate to others. Here, we evaluate how high-resolution 3D photogrammetric scanner technology can potentially allow such features to be resolved and visualised as a 3D models, which can then be shared as a taxonomical resource for species identification, as ‘virtual type specimens’, and for educational and public engagement purposes. We test the viability and limitations of this approach using specimens digitised with a Artec Micro scanner. Ten samples from unique species were mounted and scanned. The model outputs were evaluated against an identification key, which compiled diagnostic features for the specimens from the wider literature, to describe the specimens to the lowest taxonomic level possible. The results showed that six of the ten specimens could be identified to species level using the scans. Threshold values for body length and width were 10.7 mm and 4.4 mm respectively. Below these body dimensions important diagnostic features of specimens could not be resolved reliably. This result suggests that with current technology, 3D photogrammetric modelling is a viable method for taxonomic identification of a wide range of insect groups with larger body sizes. This approach opens up novel applications for species identification and data sharing among taxonomists, international field research, conservation efforts, and entomological outreach. However, the limitations of this approach to taxonomic identification must be considered depending upon the size of the specimen and its diagnostic features. Future developments in the technology and processing methods used may alleviate the constraints on body size exhibited in this study, widening the applications for smaller bodied specimens.
Oligopeptide (FK)4facilitates the determination of the absolute stereochemistry of chiral organic compoundsviaNMR Spectroscopy
Authors: Zhu Mingjun , Peng Yun , Zhang Kaihua , Wang Jiening , Yu Gangjin , Wang Guan , Wu Shan , Gong Zhou , Zhang Xu , He Lichun , Liu Maili
Published: June 2024

Molecular chirality plays a crucial role in the fields of chemistry and biology. Various nuclear magnetic resonance (NMR) methods have been employed for assignment of stereochemical configurations. Alignment media for measurements of anisotropic parameters contribute to configuration elucidations, while chiral auxiliaries assist in enantiomer discrimination and chiral recognition. However, each method comes with limitations, and the assignment of absolute configuration by NMR remains challenging. In this study, we explored a combined approach for absolute configuration elucidation with the multifaceted application of the oligopeptide (FK)4, which possesses dual functionalities as an alignment medium for anisotropic NMR measurements and a chiral differentiating agent. As an alignment medium, (FK)4facilitates the analysis of stereochemical features through residual dipolar couplings (RDC), aiding in the structural elucidation of stereoisomers. Moreover, (FK)4exhibits unique chiral differentiating properties, interacting distinctly with enantiomers and resulting in observable bifurcation of chemical shift signals, in13C,1H and19F spectra. Using isoleucine and xylose as model compounds, we demonstrate how the dual functionality of (FK)4enables the identification of stereoisomeric structuresviaRDC parameters and the assignment of enantiomeric configurations through measurements of t2 relaxation time coupled with theoretical simulations. These findings highlight the potential of versatile chiral media as (FK)4for approaching the elucidation of absolute configurations of organic moleculesviacombined NMR spectroscopy approaches, with implications for structural characterization and enantiomer discrimination in chemical applications.
Scoping review of Structured Diagnostic Interviews in the Forensic Psychiatric Setting
Authors: Bouwer Jade C , Williams Taryn , Marè Karen , Dyakalashe Nyameka , Stein Dan J
Published: June 2024

Background

Structured clinical diagnostic interviews are widely used in clinical practice and psychiatry research. Nevertheless, the extent to which such interviews have been used in forensic psychiatry is unclear, perhaps because of concerns about feasibility and utility.

Aim

We undertook a scoping review to investigate publications on structured clinical interviews in the forensic psychiatry context, paying particular attention to issues of feasibility and utility.

Methods

A PubMed and PsychInfo database search was undertaken using the terms “structured diagnostic interviews” AND “forensic psychiatry” AND “clinical attitudes” OR “utility” OR “feasibility” OR “acceptability”. PRISMA extension for Scoping Reviews (PRISMA-ScR) was used as a guideline in reviewing and including studies.

Results

We found three articles on the use of structured diagnostic interviews in the forensic psychiatry context. In most publications, these interviews were used to assess the accuracy of symptom measures using existing validation tools. There were no publications that reported on issues of feasibility and utility.

Conclusions

Literature on the use of structured diagnostic interviews in forensic psychiatry is sparse. While this may reflect concerns about feasibility and utility, no publications provide data on the feasibility and utility of such interviews in the forensic setting. This highlights an important area of research to explore.
Sequence Analysis as an approach to characterize variables that unfold over time: implementation and practical considerations for epidemiologists
Authors: Pacca Lucia , Dang Kristina V , Koenig Leah R , Duarte Catherine dP , Amina Gaye S , Harrati Amal , Vable Anusha M
Published: June 2024

Characterizing longitudinal trajectories of social exposures or health outcomes is a persistent challenge, but can be accomplished with sequence analysis, a data-driven approach that can differentiate timing, order and duration of events. We present practical guidance on implementing sequence analysis for epidemiologists with the goal of providing clear advice on decision points and tradeoffs.

We Introduce the three main steps of sequence analysis: (1) coding longitudinal processes as trajectories of ordered events for a set of individuals, (2) measuring dissimilarity between individual trajectories, and (3) performing cluster analysis to group similar trajectories. Each of these steps presents researchers with several decision points, such as data cleaning rules, options for evaluating sequence dissimilarity, and choices of clustering algorithms to group trajectories. After outlining each of the sequence analysis steps, we provide an applied example of sequence analysis in which we create and group transition-to-retirement trajectories from age 51-75 for a sample of 9,189 Health and Retirement Study participants using self-reported employment information, then estimate the association between transition-to-retirement groups and self-rated health.

Our paper seeks to guide epidemiologists through the analytic decisions and implementation challenges of sequence analysis as this approach is increasingly implemented and undergoes methodological advances.
WORKING MEMORY FILTERING AT ENCODING AND MAINTENANCE IN HEALTHY AGEING, ALZHEIMER’S AND PARKINSON’S DISEASE
Authors: Toniolo Sofia , Udale Robert , Klar Verena Svenja , Maio Maria Raquel , Attaallah Bahaaeddin , Tofaris George , Hu Michele Tao-Ming , Manohar Sanjay George , Husain Masud
Published: June 2024

The differential impact on working memory (WM) performance of distractors presented either at encoding or during maintenance was investigated in Alzheimer’s (AD), Parkinson’s Disease (PD) and healthy ageing. Across three studies, 28 AD and 28 PD patients, 28 elderly (EHC) and 28 young healthy controls (YHC) were enrolled. All participants performed a delayed reproduction task, where they reported the orientation of an arrow from a study set of either two or three items, with a distractor present either at encoding or at maintenance. Mean absolute error (the difference between probed and reported orientation) was calculated as an analogue measure of WM. Additionally, mixture model metrics i.e., memory precision, target detection, misbinding (swapping the features of an object with another probed item) and guessing were computed. MRI data was also acquired in AD, PD and EHC participants, and whole hippocampal volumes were extracted to test whether WM filtering and overall performance were related to hippocampal integrity.

EHC and PD patients showed good filtering abilities both at encoding and during maintenance. However, AD patients exhibited significant filtering deficits specifically when the distractor appearedduring maintenance.Healthy ageing and AD were associated with higher rates of both misbinding and guessing, as well as lower target detection, and memory precision. However, in healthy ageing there was a prominent decline in WM memory precision, whilst in AD lower target detection and higher guessing were the main sources of error. Conversely, PD was associated only with higher guessing rates. Hippocampal volume was significantly correlated with filtering during maintenance – but not at encoding – as well as with overall mean absolute error, target detection, guessing and misbinding. These findings demonstrate how healthy ageing and neurodegenerative diseases exhibit distinct patterns of WM impairment, including differential effects on filtering irrelevant material presented at encoding and maintenance.
Associations between prenatal caffeine exposure and child development: Longitudinal results from the Adolescent Brain Cognitive Development (ABCD) Study
Authors: Modi Hailey , Baranger David AA , Paul Sarah E , Gorelik Aaron J , Hornstein Alana , Balbona Jared V , Agrawal Arpana , Bijsterbosch Janine D , Bogdan Ryan
Published: June 2024

Objective

Though caffeine use during pregnancy is common, its longitudinal associations with child behavioral and physical health outcomes remain poorly understood. Here, we estimated associations between prenatal caffeine exposure, body mass index (BMI), and behavior as children enter adolescence.

Method

Longitudinal data and caregiver-reported prenatal caffeine exposure were obtained from the ongoing Adolescent Brain and Cognitive Development (ABCD)SMStudy, which recruited 11,875 children aged 9-11 years at baseline from 21 sites across the United States starting June 1, 2016. Prenatal caffeine exposure was analyzed as a 4-level categorical variable, and further group contrasts were used to characterize “any exposure” and “daily exposure” groups. Outcomes included psychopathology characteristics in children, sleep problems, and BMI. Potentially confounding covariates included familial (e.g., income, familial psychopathology), pregnancy (e.g., prenatal substance exposure), and child (e.g., caffeine use) variables.

Results

Among 10,873 children (5,686 boys [52.3%]; mean [SD] age, 9.9 [0.6] years) with nonmissing prenatal caffeine exposure data, 6,560 (60%) were exposed to caffeine prenatally. Relative to no exposure, daily caffeine exposure was associated with higher child BMI (β=0.08; FDR-correctedp=0.02), but was not associated with child behavior. Those exposed to two or more cups of caffeine daily (n=1,028) had greater sleep problems than those with lower/no exposure (β>0.92; FDR-correctedp<0.04).

Conclusion

Daily prenatal caffeine exposure is associated with heightened childhood BMI, and when used multiple times a day greater sleep problems even after accounting for potential confounds. Whether this relationship is a consequence of prenatal caffeine exposure or its correlated factors remains unknown.
Statistical Coupling Analysis Predicts Correlated Motions in Dihydrofolate Reductase
Authors: Kalmer Thomas L. , Ancajas Christine Mae F. , Cohen Cameron I. , McDaniel Jade M. , Oyedele Abiodun S. , Thirman Hannah L. , Walker Allison S.
Published: June 2024

The role of dynamics in enzymatic function is a highly debated topic. Dihydrofolate reductase (DHFR), due to its universality and the depth with which it has been studied, is a model system in this debate. Myriad previous works have identified networks of residues in positions near to and remote from the active site that are involved in dynamics and others that are important for catalysis. For example, specific mutations on the Met20 loop inE. coliDHFR (N23PP/S148A) are known to disrupt millisecond-timescale motions and reduce catalytic activity. However, how and if networks of dynamically coupled residues influence the evolution of DHFR is still an unanswered question. In this study, we first identify, by statistical coupling analysis and molecular dynamic simulations, a network of coevolving residues, which possess increased correlated motions. We then go on to show that allosteric communication in this network is selectively knocked down in N23PP/S148A mutantE. coliDHFR. Finally, we identify two sites in the human DHFR sector which may accommodate the Met20 loop double proline mutation while preserving dynamics. These findings strongly implicate protein dynamics as a driving force for evolution.
Gliflozins, sucrose and flavonoids are allosteric activators of lecithin:cholesterol acyltransferase
Authors: Niemelä Akseli , Giorgi Laura , Nouri Sirine , Yurttaş Betül , Rauniyar Khushbu , Jeltsch Michael , Koivuniemi Artturi
Published: June 2024

Lecithin:cholesterol acyltransferase (LCAT) serves as a pivotal enzyme in preserving cholesterol homeostasis via reverse cholesterol transport, a process closely associated with the onset of atherosclerosis. Impaired LCAT function can lead to severe LCAT deficiency disorders for which no pharmacological treatment exists. LCAT-based therapies, such as small molecule positive allosteric modulators (PAMs), against LCAT deficiencies and atherosclerosis hold promise, although their efficacy against atherosclerosis remains challenging. Herein we utilized a quantitative in silico metric to predict the activity of novel PAMs and tested their potencies with in vitro enzymatic assays. As predicted, sodium-glucose cotransporter 2 (SGLT2) inhibitors (gliflozins), sucrose and flavonoids activate LCAT. This has intriguing implications for the mechanism of action of gliflozins, which are commonly used in the treatment of type 2 diabetes, and for the endogenous activation of LCAT. Our results underscore the potential of molecular dynamics simulations in rational drug design.