bluuebunny/crossref_metadata_2025_split huggingface dataset:
Follow the Arrows: Using a Co-Created Causal Loop Diagram to Explore Leverage Points to Strengthen Population Physical Activity Promotion in British Columbia, Canada
Authors: Baugh Littlejohns Lori , McKee Geoffrey , Rasali Drona , Naiman Daniel , Mee Jennafer , Osborne Tanya , Dang Phuc , Winters Meghan , Lear Scott A. , Nelson Diane , McGinley Steve , Faulkner Guy 
Published: May 2024

Background: Population physical activity promotion (PPAP) is one of the most effective noncommunicable disease prevention strategies, yet coordination is lacking around the world. Whole-of-system approaches and complex systems methods are called for to advance PPAP. This paper reports on a project which (1) used an Attributes Framework with system mapping (group model building and causal loop diagramming of feedback loops) and (2) identified potential leverage points to address the challenge of effective coordination of multisectoral PPAP in British Columbia. Methods: Key findings from stakeholder interviews and workshops described the current system for PPAP in terms of attributes and dimensions in the framework. These were translated into variables and used in group model building. Participants prioritized the importance of variables to address the coordination challenge and then created causal loop diagrams in 3 small groups. One collective causal loop diagram was created, and top priority variables and associated feedback loops were highlighted to explore potential leverage points. Results: Leverage points included the relationships and feedback loops among priority variables: political leadership, visible policy support and governance, connectivity for knowledge translation, collaborative multisector grants, multisector collaboration, and integrating co-benefits. Leveraging and altering “vicious” cyclical patterns to increase coordinated multisector PPAP are key. Conclusions: The Attributes Framework, group model building and causal loop diagrams, and emergent feedback loops were useful to explore potential leverage points to address the challenge of multisectoral coordination of PPAP. Future research could apply the same methods in other jurisdictions and compare and contrast resultant frameworks, variables, feedback loops, and leverage points.
Engineering a coenzyme-independent dioxygenase for one-step production of vanillin from ferulic acid
Authors: Fujimaki Shizuka , Sakamoto Satsuki , Shimada Shota , Kino Kuniki , Furuya Toshiki 
Published: May 2024

ABSTRACT

Vanillin is one of the world’s most important flavor and fragrance compounds used in foods and cosmetics. In plants, vanillin is reportedly biosynthesized from ferulic acid via the hydratase/lyase-type enzyme VpVAN. However, in biotechnological and biocatalytic applications, the use of VpVAN limits the production of vanillin. Although microbial enzymes are helpful as substitutes for plant enzymes, synthesizing vanillin from ferulic acid in one step using microbial enzymes remains a challenge. Here, we developed a single enzyme that catalyzes vanillin production from ferulic acid in a coenzyme-independent manner via the rational design of a microbial dioxygenase in the carotenoid cleavage oxygenase family using computational simulations. This enzyme acquired catalytic activity toward ferulic acid by introducing mutations into the active center to increase its affinity for ferulic acid. We found that the single enzyme can catalyze not only the production of vanillin from ferulic acid but also the synthesis of other aldehydes from
p
-coumaric acid, sinapinic acid, and coniferyl alcohol. These results indicate that the approach used in this study can greatly expand the range of substrates available for the dioxygenase family of enzymes. The engineered enzyme enables efficient production of vanillin and other value-added aldehydes from renewable lignin-derived compounds.

IMPORTANCE
The final step of vanillin biosynthesis in plants is reportedly catalyzed by the enzyme VpVAN. Prior to our study, VpVAN was the only reported enzyme that directly converts ferulic acid to vanillin. However, as many characteristics of VpVAN remain unknown, this enzyme is not yet suitable for biocatalytic applications. We show that an enzyme that converts ferulic acid to vanillin in one step could be constructed by modifying a microbial dioxygenase-type enzyme. The engineered enzyme is of biotechnological importance as a tool for the production of vanillin and related compounds via biocatalytic processes and metabolic engineering. The results of this study may also provide useful insights for understanding vanillin biosynthesis in plants.
Repression of
Acinetobacter baumannii
DNA damage response requires DdrR-assisted binding of UmuDAb dimers to atypical SOS box
Authors: Candra Belinda , Cook Deborah , Hare Janelle 
Published: May 2024

ABSTRACT

The DNA damage response of the multi-drug-resistant nosocomial pathogen
Acinetobacter baumannii
possesses multiple features that distinguish it from the commonly used LexA repression system. These include the absence of LexA in this genus, the evolution of a UmuD polymerase manager into the UmuDAb repressor of error-prone polymerases, the use of a corepressor unique to
Acinetobacter
(DdrR), and an unusually large UmuDAb binding site. We defined cis- and trans-acting factors required for UmuDAb DNA binding and gene repression, and tested whether DdrR directly enhances its DNA binding. We used DNA binding assays to characterize UmuDAb’s binding to its proposed operator present upstream of the six co-repressed
umuDC
or
umuC
genes. UmuDAb bound tightly and cooperatively to this site with ~10-fold less affinity than LexA. DdrR enhanced the binding of both native and dimerization-deficient UmuDAb forms, but only in greater than equimolar ratios relative to UmuDAb. UmuDAb mutants unable to dimerize or effect gene repression showed impaired DNA binding, and a strain expressing the G124D dimerization mutant could not repress transcription of the UmuDAb-DdrR regulon. Competition electrophoretic mobility shift assays conducted with mutated operator probes showed that, unlike typical SOS boxes, the UmuDAb operator possessed a five-base pair central core whose sequence was more crucial for binding than the flanking palindrome. The presence of only one of the two flanking arms of the palindrome was necessary for UmuDAb binding. Overall, the data supported a model of an operator with two UmuDAb binding sites. The distinct characteristics of UmuDAb and its regulated promoters differ from the typical LexA repression model, demonstrating a novel method of repression.

IMPORTANCE

Acinetobacter baumannii
is a gram-negative bacterium responsible for hospital-acquired infections. Its unique DNA damage response can activate multiple error-prone polymerase genes, allowing it to gain mutations that can increase its virulence and antibiotic resistance. The emergence of infectious strains carrying multiple antibiotic resistance genes, including carbapenem resistance, lends urgency to discovering and developing ways to combat infections resistant to treatment with known antibiotics. Deciphering how the regulators UmuDAb and DdrR repress the error-prone polymerases could lead to developing complementary treatments to halt this mechanism of generating resistance.
Mental health in student-athletes in Norwegian lower secondary sport schools
Authors: Saarinen Milla , Phipps Daniel John , Bjørndal Christian Thue 
Published: May 2024

ObjectivesThe Norwegian sport school system offers a method for helping young dual-career athletes achieve their best both in academia and sports. However, there remains a concern that pursuing dual careers at a young age may leave some student-athletes vulnerable to poor mental health outcomes. The aim of this study was to investigate the association between gender, grade, and sport type and problematic scores on school burn-out, sport burn-out, self-esteem and psychological distress in student-athletes within a sample of Norwegian lower secondary schools.MethodsA sample of 642 student-athletes (ages 12–14) in grades 8–10 across 8 Norwegian lower secondary sport schools completed questionnaires on burn-out, self-esteem and psychological distress at the beginning of the school year.ResultsFemales were more likely to report high levels of sport-related burn-out and psychological distress, and low self-esteem; older student-athletes were more likely to report severe school-related and sport-related burn-out; and individual sport student-athletes were more likely to report high levels of psychological distress.ConclusionsLower secondary sport schools in Norway may seek to be aware of the challenges facing student-athletes for informed practical steps to protect their mental health and maximise their outcomes as school students and athletes.
Effects of Brownian motion on solitary wave structures for 1D stochastic Poisson–Nernst–Planck system in electrobiochemical
Authors: Nan Tang , Baber Muhammad Zafarullah , Ahmed Nauman , Iqbal Muhammad Sajid , Demirbilek Ulviye , Rezazadeh Hadi 
Published: May 2024

This study deals with the time fractional 1D stochastic Poisson–Nernst–Planck (TFSPNP) system under the effect of multiplicative time noise. The M-truncated derivative (MTD) takes into consideration the fractional order time derivative. This is a steady-state Poisson–Nernst–Planck (PNP) equations that have applications in bioelectric dressings and bandages. To obtain the soliton solutions of TFSPNP, we use the generalized exponential rational functional method. These findings are presented in the form of trigonometric, exponential, and hyperbolic functions. Moreover, to show the effect of multiplicative time noise and MTD, we construct the plot of some solutions in the form of three-dimensional, two-dimensional, and their corresponding contours. These plots clearly show the effect of randomness in the wave structures for the exact solitary wave solutions that are attained. In general, the solutions become more stable when a noise term disrupts their symmetry.
Key Information Extraction and Recognition from Rich Text Images
Authors: Do Tien , Doan Thuyen Tran , Le Khiem , Nguyen Thua , Le Duy-Dinh , Ngo Thanh Duc 
Published: May 2024

Key information extraction and recognition from rich text images are crucial for various applications. There are two main tasks involved in this process: Line Item Recognition (LIR) and Key Information Localization and Extraction (KILE). LIR aims at identifying and interpreting data line items in a document. The essential information in each line item is then classified or extracted, a task known as KILE. A widely used approach for this problem is sequence based, which relies on the generalization of a language model and requires a significant amount of training time. We present an effective and reliable solution to the problem by using RoBERTa, a transformer model trained on a large corpus, along with the LION optimizer to improve the training process. A comprehensive evaluation was conducted on two different benchmarks, emphasizing two different languages, English and Vietnamese. Experimental results on DocILE indicate that the proposed framework significantly improves the KILE task with a 7.24% increase in accuracy compared to the baseline and also enhances the correct recognition rate at the LIR stage. On MCOCR, the method achieved a Character Error Rate (CER) of 28.6%, which is competitive with the state-of-the-art on this dataset.
Like Father, Like Daughter – Ectodermal Dysplasia-Syndactyly Syndrome: A Case Report
Authors: JITH Gopika , SUBA Santanu , GIRI Sanjay Kumar 
Published: May 2024

Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) is an exceedingly rare condition associated with mutations in the PVL4 gene. It is characterised by sparse, brittle hair, eyebrows and eyelashes, abnormal dentition and nails, along with bilateral cutaneous syndactyly involving the fingers and toes. We report a 2-year-old girl who presented to us with bilateral complete simple syndactyly of the third and fourth web spaces of the hands, along with bilateral syndactyly of both feet involving the second to fourth toes. Upon examination, sparse hair and eyebrows, along with abnormal dentition, were noted. Thorough clinical examination and genetic analysis were conducted on the affected child and her father, who exhibited similar clinical features. Genetic analysis revealed a homozygous nonsense mutation in the PVL4 gene in both individuals. According to the literature, EDSS1 has been reported in only 10 families worldwide, and there are no reported cases from India. Level of Evidence: Level V (Therapeutic)
Kidney Cancer Incidence among Non-Hispanic American Indian and Alaska Native Populations in the United States, 1999 to 2020
Authors: Melkonian Stephanie C. , Jim Melissa A. , Haverkamp Donald , Lee Madeleine , Janitz Amanda E. , Campbell Janis E. 
Published: May 2024

Abstract

Background:
Non-Hispanic American Indian and Alaska Native (NH-AI/AN) people exhibit a disproportionate incidence of kidney cancer. Nationally aggregated data do not allow for a comprehensive description of regional disparities in kidney cancer incidence among NH-AI/AN communities. This study examined kidney cancer incidence rates and trends among NH-AI/AN compared with non-Hispanic White (NHW) populations by geographic region.

Methods:
Using the United States Cancer Statistics American Indian and Alaska Native (AI/AN) Incidence Analytic Database, age-adjusted incidence rates (per 100,000) of kidney cancers for NH-AI/AN and NHW people for the years 2011 to 2020 combined using surveillance, epidemiology, and end Results (SEER)∗stat software. Analyses were restricted to non-Hispanic individuals living in purchased/referred care delivery area (PRCDA) counties. Average annual percent changes (AAPCs) and trends (1999–2019) were estimated using Joinpoint regression analyses.

Results:
Rates of kidney cancer incidence were higher among NH-AI/AN compared with NHW persons in the United States overall and in five of six regions. Kidney cancer incidence rates also varied by region, sex, age, and stage of diagnosis. Between 1999 and 2019, trends in kidney cancer rates significantly increased among NH-AI/AN males (AAPC = 2.7%) and females (AAPC = 2.4%). The largest increases were observed for NH-AI/AN males and females aged less than 50 years and those diagnosed with localized-stage disease.

Conclusions:
Study findings highlight growing disparities in kidney cancer incidence rates between NH-AI/AN and NHW populations.

Impact:
Differences in geographic region, sex, and stage highlight the opportunities to decrease the prevalence of kidney cancer risk factors and improve access to preventive care.
Plasma versus Tissue Tumor Mutational Burden as Biomarkers of Durvalumab plus Tremelimumab Response in Patients with Metastatic Colorectal Cancer in the CO.26 Trial
Authors: Loree Jonathan M. , Titmuss Emma , Topham James T. , Kennecke Hagen F. , Feilotter Harriet , Virk Shakeel , Lee Young S. , Banks Kimberly , Quinn Katie , Karsan Aly , Renouf Daniel J. , Jonker Derek J. , Tu Dongsheng , O’Callaghan Chris J. , Chen Eric X. 
Published: May 2024

Abstract

Purpose:
Tissue-derived tumor mutation burden (TMB) of ≥10 mutations/Mb is a histology-agnostic biomarker for the immune checkpoint inhibitor (ICI) pembrolizumab. However, the dataset in which this was validated lacked colorectal cancers (CRC), and there is limited evidence for immunotherapy benefits in CRC using this threshold.

Patients and Methods:
CO.26 was a randomized phase II study of 180 patients, comparing durvalumab and tremelimumab (D + T, n = 119 patients) versus best supportive care (BSC; n = 61 patients). ctDNA sequencing was available for 168 patients (n = 118 D + T; n = 50), of whom 165 had evaluable plasma TMB (pTMB). Tissue sequencing was available for 108 patients. Optimal thresholds for stratifying patients based on OS were determined using a minimal P value approach. This report includes the final OS analysis.

Results:
Tissue TMB ≥10 mutations/Mb was not predictive of benefit from D + T compared with BSC in microsatellite stable (MSS) metastatic CRC [HR, 0.71 (95% CI, 0.28–1.80); P = 0.47]. No tissue TMB threshold could identify a high TMB group that benefited from ICI. By contrast, plasma TMB (pTMB) ≥28 mutations/Mb was predictive of benefit from D + T [HR, 0.34 (95% CI, 0.13–0.85); P = 0.022], as was clonal pTMB ≥10.6 mutations/Mb [HR, 0.10 (95% CI, 0.014–0.79); P = 0.029] and subclonal pTMB ≥25.9/Mb [HR, 0.20 (95% CI, 0.061–0.69); P = 0.010]. Higher pTMB was associated with length of time on cytotoxic agents (P = 0.021) and prior anti-EGFR exposure (P = 2.44 × 10−06).

Conclusions:
pTMB derived from either clonal or subclonal mutations may identify a group likely to benefit from immunotherapy, although validation is required. Tissue TMB provided no predictive utility for immunotherapy in this trial.
S100a8/9 (S100 Calcium Binding Protein a8/9) Promotes Cardiac Hypertrophy Via Upregulation of FGF23 (Fibroblast Growth Factor 23) in Mice
Authors: Yuan Yu‐Pei , Shen Zhuo‐Yu , Teng Teng , Xu Si‐Chi , Kong Chun‐Yan , Zeng Xiao‐Feng , A. Hofmann Bowman Marion , Yan Ling 
Published: May 2024

Background
S100a8/9 (S100 calcium binding protein a8/9) belongs to the S100 family and has gained a lot of interest as a critical regulator of inflammatory response. Our previous study found that S100a8/9 homolog promoted aortic valve sclerosis in mice with chronic kidney disease. However, the role of S100a8/9 in pressure overload‐induced cardiac hypertrophy remains unclear. The present study was to explore the role of S100a8/9 in cardiac hypertrophy.

Methods and Results
Cardiomyocyte‐specific S100a9 loss or gain of function was achieved using an adeno‐associated virus system, and the model of cardiac hypertrophy was established by aortic banding‐induced pressure overload. The results indicate that S100a8/9 expression was increased in response to pressure overload. S100a9 deficiency alleviated pressure overload‐induced hypertrophic response, whereas S100a9 overexpression accelerated cardiac hypertrophy. S100a9‐overexpressed mice showed increased FGF23 (fibroblast growth factor 23) expression in the hearts after exposure to pressure overload, which activated calcineurin/NFAT (nuclear factor of activated T cells) signaling in cardiac myocytes and thus promoted hypertrophic response. A specific antibody that blocks FGFR4 (FGF receptor 4) largely abolished the prohypertrophic response of S100a9 in mice.

Conclusions
In conclusion, S100a8/9 promoted the development of cardiac hypertrophy in mice. Targeting S100a8/9 may be a promising therapeutic approach to treat cardiac hypertrophy.
Prognostic Value of Objective Social Isolation and Loneliness in Older Patients With Heart Failure: Subanalysis of FRAGILE‐HF and Kitasato Cohort
Authors: Saito Hiroshi , Maeda Daichi , Kagiyama Nobuyuki , Sunayama Tsutomu , Dotare Taishi , Fujimoto Yudai , Jujo Kentaro , Saito Kazuya , Uchida Shota , Hamazaki Nobuaki , Kamiya Kentaro , Ogasahara Yuki , Maekawa Emi , Konishi Masaaki , Kitai Takeshi , Iwata Kentaro , Wada Hiroshi , Kasai Takatoshi , Nagamatsu Hirofumi , Ako Junya , Momomura Shin‐ichi , Matsue Yuya 
Published: May 2024

Background
Social factors encompass a broad spectrum of nonmedical factors, including objective (social isolation [SI]) and perceived (loneliness) conditions. Although social factors have attracted considerable research attention, information regarding their impact on patients with heart failure is scarce. We aimed to investigate the prognostic impact of objective SI and loneliness in older patients with heart failure.

Methods and Results
This study was conducted using the FRAGILE‐HF (Prevalence and Prognostic Value of Physical and Social Frailty in Geriatric Patients Hospitalized for Heart Failure; derivation cohort) and Kitasato cohorts (validation cohort), which included hospitalized patients with heart failure aged ≥65 years. Objective SI and loneliness were defined using the Japanese version of Lubben Social Network Scale‐6 and diagnosed when the total score for objective and perceived questions on the Lubben Social Network Scale‐6 was below the median in the FRAGILE‐HF. The primary outcome was 1‐year death. Overall, 1232 and 405 patients in the FRAGILE‐HF and Kitasato cohorts, respectively, were analyzed. Objective SI and loneliness were observed in 57.8% and 51.4% of patients in the FRAGILE‐HF and 55.4% and 46.2% of those in the Kitasato cohort, respectively. During the 1‐year follow‐up, 149 and 31 patients died in the FRAGILE‐HF and Kitasato cohorts, respectively. Cox proportional hazard analysis revealed that objective SI, but not loneliness, was significantly associated with 1‐year death after adjustment for conventional risk factors in the FRAGILE‐HF. These findings were consistent with the validation cohort.

Conclusions
Objective SI assessed using the Lubben Social Network Scale‐6 may be a prognostic indicator in older patients with heart failure. Given the lack of established SI assessment methods in this population, further research is required to refine such methods.
Five‐Year Cumulative Cardiovascular Health and Clinical Events in Patients With Chronic Kidney Disease: The CRIC Study
Authors: Cao Qiuyu , Bi Yufang , Alvarado Flor , Anderson Amanda H. , Mills Katherine T. , Jaeger Byron C. , Chen Jing , He Jiang , Bundy Joshua D. , Appel Lawrence J. , Cohen Debbie , Dember Laura M. , Go Alan S. , Lash James P. , Nelson Robert G. , Rahman Mahboob , Rao Panduranga S. , Shah Vallabh O. , Unruh Mark L. 
Published: May 2024

Background
Higher cardiovascular health (CVH) score is associated with lower risks of cardiovascular disease (CVD) and mortality in the general population. However, it is unclear whether cumulative CVH is associated with CVD, end‐stage kidney disease (ESKD), and death in patients with chronic kidney disease.

Methods and Results
Among individuals from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we used the percentage of the maximum possible CVH score attained from baseline to the year 5 visit to calculate cumulative CVH score. Multivariable‐adjusted Cox proportional hazards regression was used to investigate the associations of cumulative CVH with risks of adjudicated CVD (myocardial infarction, stroke, and heart failure), ESKD, and all‐cause mortality. A total of 3939 participants (mean age, 57.7 years; 54.9% men) were included. The mean (SD) cumulative CVH score attained during 5 years was 55.5% (12.3%). Over a subsequent median 10.2‐year follow‐up, 597 participants developed CVD, 656 had ESKD, and 1324 died. A higher cumulative CVH score was significantly associated with lower risks of CVD, ESKD, and mortality, independent of the CVH score at year 5. Multivariable‐adjusted hazard ratios and 95% CIs per 10% higher cumulative CVH score during 5 years were 0.81 (0.69–0.95) for CVD, 0.82 (0.70–0.97) for ESKD, and 0.80 (0.72–0.89) for mortality.

Conclusions
Among patients with chronic kidney disease stages 2 to 4, a better CVH status maintained throughout 5 years is associated with lower risks of CVD, ESKD, and all‐cause mortality. The findings support the need for interventions to maintain ideal CVH status for prevention of adverse outcomes in the population with chronic kidney disease.