bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between exposure to air pollution and increased ischaemic stroke incidence: a retrospective population-based cohort study (EP-PARTICLES study)
Authors: Święczkowski Michał , Lip Gregory Y H , Kurasz Anna , Dąbrowski Emil J , Tomaszuk-Kazberuk Anna , Kamiński Jacek W , Strużewska Joanna , Dobrzycki Sławomir , Kuźma Łukasz
Published: September 2024

Aims

Short-term effects of Polish smog, particularly benzo(alpha)pyrene [B(a)P], are unclear. We aimed to examine the association between short-term exposure to air pollution and ischaemic stroke (IS) incidence.

Methods and results

We conducted a retrospective population-based cohort study including an EP-PARTICLES cohort of 8 million inhabitants in the years 2011–20 (80 million person-years of observation). Individual clinical data on emergency hospitalizations due to IS (ICD-10: I63.X) was analysed. We used quasi-Poisson models to examine municipality-specific associations between air pollutants and IS, considering various covariates. We recorded 146 262 cases of IS with a dominance of females (51.8%) and people over 65 years old (77.6%). In the overall population, exposure to PM2.5, NO2, B(a)P, and SO2 increased the risk of IS onset on the day of exposure by 2.4, 1, 0.8, and 0.6%, respectively. Age and sex were modifying variables for PM2.5, NO2, and B(a)P exposure with more pronounced effects in non-elderly individuals and women (all Pinteraction < 0.001). Residents of regions with high tobacco and alcohol consumption were more sensitive to the effects of PM2.5 and SO2. The slopes of response–effect curves were non-linear and steeper at lower concentrations.

Conclusion

Exposure to air pollution may be associated with higher IS incidence, particularly posing a higher risk to non-elderly women. Harmful lifestyle habits might exacerbate its impact. Exposure to even low levels of air pollutants had negative effects.

Registration

The study was registered at ClinicalTrials.gov (NCT05198492).
Female participation, and sex-specific reporting practices, in polypill randomized controlled trials in the prevention of atherosclerotic cardiovascular disease: a secondary analysis of a systematic review
Authors: Peters Sanne A E , Rodgers Anthony , Patel Anushka , Norton Robyn , Huffman Mark D , Agarwal Anubha
Published: September 2024

Aims

The polypill is an emerging strategy for the prevention and management of cardiovascular disease (CVD). We assessed the participation of females in randomized controlled trials evaluating polypills for prevention of CVD and subsequent sex-specific analyses and reporting.

Methods and results

Cardiovascular polypill trials were identified through a systematic review. Data were extracted on the use of sex-specific eligibility criteria, female participation, and the conduct, findings, and interpretation of sex-specific analyses. Of 26 trials included, 12 (46%) excluded groups of females, mainly if pregnant or lactating or of childbearing potential. Female participation ranged from 10% to 73% across trials. Overall, 42% of included participants were female. Of 18 trials conducted in a mostly primary prevention population, females represented 49% of trial participants. In mixed or exclusively secondary prevention trials (n = 8), females represented 26% of trial participants. Females represented 46% of trial participants in trials that excluded groups of females (n = 12). In trials without explicit exclusion criteria (n = 13), females represented 32% of trial participants. Nine out of 26 trials reported sex-stratified analyses (35% of trials; 70% of all participants). Of these, two found some evidence for possible sex differences, both reporting larger blood pressure effects in females than males. Four trials provided sex considerations in the discussion section of the report.

Conclusion

The participation of females in cardiovascular polypill trials is substantially higher in primary prevention trials as compared with trials conducted in mixed or exclusively secondary prevention populations. The use of sex-specific eligibility criteria was not linked to lower female participation. Sex-specific reporting is sparsely conducted, although most frequent in larger trials.
I have a question about evaluative reporting: a comprehensive collection of FAQs
Authors: Ostrum Ronald Brent
Published: September 2024

With various calls in the forensic scientific literature for pattern-matching disciplines to adopt evaluative reporting, which is also known as the likelihood ratio or logical approach, practitioners used to reporting evidence under a more traditional paradigm may have a level of apprehension and face a steep learning curve. There may be doubts about the benefits of evaluative reporting, when it applies and when it does not, what it actually entails, its validity, and how to explain it in court. These questions and more are answered in this comprehensive collection of frequently asked questions on evaluative reporting. While the focus is on providing context for forensic handwriting examiners, many of the questions and answers are general in nature and the concepts can be applied to other disciplines.
An efficient algorithm for gravity forward modelling (GFM) with masses of arbitrary shapes and density distributions
Authors: Chen Wenjin , Tan Xiaolong
Published: September 2024

Currently, gravimetric forward modelling of mass density structures with arbitrary geometries and density distributions typically involves subdividing the mass body into individual geometric elements (such as rectangular prisms), calculating their gravitational contributions that are then summed up to obtain the gravitational attraction of the whole body. To achieve a more accurate approximation of the true geometric shape and density distribution, this rectangular prism model requires fine dividing, which significantly increases computational load and reduces numerical efficiency. To address this issue, we propose the algorithm for gravimetric forward modelling of arbitrary geometric shapes and density distributions in spectral domain that significantly improves numerical efficiency while preserves computational accuracy. The novelty of our proposed algorithm lies in dividing the masses into multiple layers of equal thickness in the vertical direction, providing constant upper and lower bounds. This allows to extended Parker's formulas and apply the Fast Fourier Transform to increase numerical efficiency. The algorithm is tested using synthetic models and then used to compute gravitational effects of topography and sediments using real data from Tibet. Results show high accuracy and numerical efficiency than rectangular prism approach.
Chromatin accessibility profile and the role of PeAtf1 transcription factor in the postharvest pathogen Penicillium expansum
Authors: Wang Yiran , Wang Kaili , Yang Qiya , Wang Zhaoting , Su Yingying , Chen Xifei , Zhang Hongyin
Published: September 2024

Gene transcription is governed by a complex regulatory system involving changes in chromatin structure, the action of transcription factors, and the activation of cis-regulatory elements. Postharvest fruits are threatened by Penicillium expansum, a leading causal agent of blue mold disease and one of the most economically significant postharvest pathogens worldwide. However, information on its transcription regulatory mechanism is lagging. Here, we conducted an assay for transposase accessible chromatin sequencing (ATAC-seq) for P. expansum during vegetative growth and infection phase and then studied the function of a basic leucine zipper (bZIP) transcription factor PeAtf1. Results highlighted the role of promoter regions in gene transcription and the significant difference in P. expansum between these two phases. Six footprint-supported cis-regulatory elements of active transcription factors were obtained and analyzed. We then identified a homolog of the bZIP regulator Atf1, PeAtf1, and found it positively regulated vegetative growth, reproduction, and osmotic stress response in P. expansum. Furthermore, PeAtf1 deletion enhanced the fungus's tolerance to oxidative, cell wall, and membrane stresses, which might contribute to the virulence of deletion mutants in apple fruits, leading to similar pathogenicity between mutants and the wild type. Overall, this study provides new insights into the transcription regulatory profile of P. expansum, aiding in the future development of strategies to control P. expansum.
Oligo-FISH barcode chromosome identification system provides novel insights into the natural chromosome aberrations propensity in the autotetraploid cultivated alfalfa
Authors: Meng Zhuang , Zheng Qian , Wang Wei , Zhu Yuanbin , Li Yuanhao , Dong Fulin , Luo Wenjun , Zhang Zhiliang , Wang Fei , Shen Haitao , Xie Quanliang , Li Hongbin
Published: September 2024

Alfalfa is one of the most economically valuable forage crops in the world. However, molecular cytogenetic studies in alfalfa lag far behind other cash crops and have reached a bottleneck. Here, we developed a novel chromosome identification system by designing 21 oligo probes in specific regions of each chromosome, which can be used as a barcode to simultaneously distinguish all chromosomes in a cell. Using this system, we revealed the chromosome karyotype features and evolutionary differences among 10 cultivated alfalfa varieties. Interestingly, we also found two chromosomal variation types, i.e. aneuploidy and large chromosomal segment deletions in the seeds of three alfalfa varieties. Variation frequency analysis showed that only 7/173 seeds in those three alfalfa varieties had chromosome aberrations, which indicated that the inheritance and meiosis of alfalfa had evolved to a relatively stable state. Remarkably, 4/7 variation seeds were chromosome 2 aberrations, suggesting that chromosome 2 appears to be more susceptible to natural chromosomal aberrations than other chromosomes during inheritance. DNA sequence variation analysis showed that the difference of presence and absence variations (PAVs) among homologous copies of chromosome 2 was larger than that of the other seven chromosomes. We suggest that such large PAV divergence among homologous copies may provide the physical basis for natural chromosome 2 aberrations propensity. Our study provides a valuable and efficient tool for alfalfa’s molecular cytogenetics and sheds new insights into the propensity for natural chromosome aberrations during autopolyploid inheritance.
Care as a constitutional value
Authors: Fredman Sandra
Published: September 2024

This article explores the potential of regarding care as a constitutional issue, rather than addressing it solely through legislation, the family, or the market. It is argued that care is best regarded as a constitutional value, reflecting the reality of our interdependence, and functioning as a crucial counterweight to the fiction that individual freedom can be constituted independently of our social relations. Care as a constitutional value should be regarded as complementing express constitutional commitments to freedom, dignity, and equality, recognizing that relationships are constitutive of the self, and that individuals are partly constituted by society. Just as freedom, dignity, and equality perform important expressive functions in a constitution, so the recognition of care, implicit or explicit, signals the foundational importance of care to everyone throughout our lives and to society’s ability to reproduce itself. Care as a constitutional value should permeate the interpretation of constitutional and other provisions, and enhance accountability for care-related decisions, encouraging decision-makers to pay attention to care, and prompting courts to interpret constitutional and legislative measures with the value of care in mind. In this way, the gaps in welfare law, labor law, and free market regulation can be addressed to face the challenges of care. Equally importantly, care as a constitutional value can act as a catalyst for political activism, legitimizing grassroots campaigns for better recognition of care. This article is normative and exploratory. At the same time, its propositions are tested against constitutional jurisprudence in India, South Africa, Canada, and the United Kingdom.
Bi-stochastically normalized graph Laplacian: convergence to manifold Laplacian and robustness to outlier noise
Authors: Cheng Xiuyuan , Landa Boris
Published: September 2024

Bi-stochastic normalization provides an alternative normalization of graph Laplacians in graph-based data analysis and can be computed efficiently by Sinkhorn–Knopp (SK) iterations. This paper proves the convergence of bi-stochastically normalized graph Laplacian to manifold (weighted-)Laplacian with rates, when $n$ data points are i.i.d. sampled from a general $d$-dimensional manifold embedded in a possibly high-dimensional space. Under certain joint limit of $n \to \infty $ and kernel bandwidth $\epsilon \to 0$, the point-wise convergence rate of the graph Laplacian operator (under 2-norm) is proved to be $ O( n^{-1/(d/2+3)})$ at finite large $n$ up to log factors, achieved at the scaling of $\epsilon \sim n^{-1/(d/2+3)} $. When the manifold data are corrupted by outlier noise, we theoretically prove the graph Laplacian point-wise consistency which matches the rate for clean manifold data plus an additional term proportional to the boundedness of the inner-products of the noise vectors among themselves and with data vectors. Motivated by our analysis, which suggests that not exact bi-stochastic normalization but an approximate one will achieve the same consistency rate, we propose an approximate and constrained matrix scaling problem that can be solved by SK iterations with early termination. Numerical experiments support our theoretical results and show the robustness of bi-stochastically normalized graph Laplacian to high-dimensional outlier noise.
Sustainability performance of food supply chains with internal and external evaluation perspectives
Authors: Gürül Binnur , Yilmaz Dilek , Kiriş Sinem Büyüksaatçı
Published: September 2024

Accepted by: M. Zied Babai

The challenges of food security, water use, energy consumption and the growing global demand for food raise the importance of ensuring sustainability of the food supply chains (FSCs). Studies in relevant literature discuss the sustainability performances of FSCs generally without distinguishing between the internal and external stakeholders’ concerns or clarifying the existence of greenwashing or bluewashing attempts, jeopardizing true sustainability. This is why modelling towards some holistic treatment of the problem that satisfies those concerns is required. This paper proposes a framework to evaluate the true sustainability performance of FSCs by considering triple bottom line indicators, i.e. economic, environmental and social. In light of the proposed framework, two models have been developed, one calculating the internal and the other an external sustainability score. The presented models can handle interval or ordinal qualitative and quantitative indicators concurrently while considering desirable and undesirable factors. These novel models have been implemented on data from 50 FSCs in Istanbul, using a two-stage imprecise data envelopment analysis with a special multiplier. To facilitate visualization of true sustainability assessment, an internal–external sustainability performance matrix is proposed. Results reveal that the internal sustainability performance of the focal FSCs is better than the external one. The economic dimension predominates in Turkish FSCs’ internal sustainability performance, while the environmental and social dimensions predominate in the external sustainability performance of the FSCs.
Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection
Authors: Chou Sunwen , Winston Drew J , Avery Robin K , Cordonnier Catherine , Duarte Rafael F , Haider Shariq , Maertens Johan , Peggs Karl S , Solano Carlos , Young Jo-Anne H , Gu Joan , Pocock Ginger , Papanicolaou Genovefa A
Published: September 2024

Background

Among 547 patients receiving maribavir or valganciclovir for first-episode cytomegalovirus infection after hematopoietic cell transplant, the treatment response rate was 69.6% and 77.4% respectively. Development of maribavir and ganciclovir resistance was compared after receiving either drug.

Methods

Viral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and posttreatment.

Results

Prior antiviral drug exposure was limited, with only 2 instances of baseline drug resistance detected. An equal number (n = 241) received valganciclovir or maribavir for at least 21 days (median, 55–56 days). Among them, drug resistance mutations were detected in 24 (10%) maribavir recipients at 35–125 days (median, 56 days) after starting therapy, including in 12 of 14 who experienced a viral load rebound while on therapy. Ganciclovir resistance mutations developed in 6 (2.5%) valganciclovir recipients at 66–110 days (median, 90 days). One maribavir recipient developed a novel UL97 gene mutation (P-loop substitution G343A) that conferred strong maribavir and ganciclovir resistance in vitro. Viral clearance was confirmed in 17 (74%) of 23 patients with emergent maribavir resistance after retreatment with an alternative CMV antiviral drug.

Conclusions

After 3–8 weeks of therapy, maribavir resistance emerged earlier and more frequently than ganciclovir resistance but was usually treatable using alternative therapy.

Clinical Trials Registration. NCT02927067 (AURORA).
Bacillus subtilis B55 degraded the ferulic acid and p-coumaric acid and changed the soil bacterial community in soils
Authors: Liu Dongli , Ge Xin , Pan Dandan , Zheng Xianqing , Zhou Xingang
Published: September 2024

Aims

This study aimed to assess the effects of phenolic acid-degrading bacteria strains on phenolic acid content, plant growth, and soil bacterial community in phenolic acid-treated soils.

Methods and results

The strain of interest coded as B55 was isolated from cucumber root litter, and its degradation rates of ferulic acid and p-coumaric acid were 81.92% and 72.41% in Luria-Bertani solution, respectively, and B55 was identified as Bacillus subtilis. B55 had plant growth-promoting attributes, including solubilization of inorganic phosphate and production of siderophore and indole acetic acid. Both ferulic acid and p-coumaric acid significantly restrained an increase in cucumber seedling dry biomass, while the B55 inoculation not only completely counteracted the damage of phenolic acids to cucumber seedlings and decreased the content of ferulic acid and p-coumaric acid in soil, but also promoted cucumber seedlings growth. Amplicon sequencing found that B55 inoculation changed the cucumber rhizosphere bacterial community structure and promoted the enrichment of certain bacteria, such as Pseudomonas, Arthrobacter, Bacillus, Flavobacterium, Streptomyces, and Comamonas.

Conclusions

B55 not only promoted cucumber seedling growth, and decreased the content of ferulic acid and p-coumaric acid in soil, but it also increased the relative abundance of beneficial microorganisms in the cucumber rhizosphere.
Enhancing skeletal muscle fiber characteristics, intramuscular fat deposition, and fatty acid composition in broilers under heat stress through combined selenomethionine and Bacillus subtilis supplementation in the diet
Authors: Yang Weiguang , Xue Junjing , Zhang Sha , Yao Chenge , Zhang Na , Fang Rejun
Published: September 2024

Heat stress is the most common environmental stressor in poultry production, negatively affecting growth performance, meat quality, and welfare. Therefore, the aim of this study was to compare the nutritional effects of dietary supplementation with selenomethionine, Bacillus subtilis (BS), and a combination of selenomethionine and BS on broilers challenged with heat stress. A total of 300 21-day-old male broilers (Ross 308) were randomly assigned to 5 groups with 6 replicates of 10 broilers per each: control group (CON, broilers raised at 22 ± 2 °C), heat stress exposure group (HS, broilers raised at 32 ± 2 °C for 8 h/d), HSS group (HS group supplemented with 0.3 mg/kg selenomethionine), HSB group (HS group supplemented with 1 × 109 cfu/kg BS), and HSBS group (HS group supplemented with 0.3 mg/kg selenomethionine and × 109 cfu/kg BS). The experiment lasted for 21 d. The results indicated that, compared to the CON group, heat stress reduces (P < 0.05) broiler growth performance and damages the meat quality in breast and thigh muscles. Dietary supplementation with selenomethionine and BS did not improve the growth performance of broilers under heat stress. However, compared to the HS group, the HSS, HSB, and HSBS groups showed significantly increased (P < 0.05) pH45 min, redness (a*) and yellowness (b*), muscle fiber density, intramuscular fat, triglyceride content, and expression levels of Myf5, CAPN 2, FM, SLC27A1, A-FABP, H-FABP, APOB-100, and ACC in breast and thigh muscles. Meanwhile, these groups showed reduced (P < 0.05) lightness (L*), drip loss, shear force, muscle fiber cross-sectional area, and FM gene expression level. The HSBS group showed greater improvement in the physicochemical quality of muscle and volatile substances compared to the HSS and HSB groups. In conclusion, selenomethionine and BS improved meat quality and flavor in broilers under heat stress by modulating muscle fiber composition and characteristics, as well as increasing intramuscular fat deposition.
Safety of Silver Dressings in Infants; a Systematic Scoping Review
Authors: O’Donohoe Patrick K , Leon Ryan , Orr David J A , de Blacam Catherine
Published: September 2024

Silver-based dressings are used to reduce infection risk and optimize conditions for wound healing. They are widely used in the management of burns and other complex wounds. However, reports of elevated serum silver and concern over systemic toxicity have meant that their use in young children has been questioned. The aim of the current study was to map the literature relating to the use of silver-based dressings in children under 1 year of age. A systematic scoping review was conducted according to the methodology described by the Joanna Briggs Institute. Sources were identified from major medical databases as well as the gray literature. Inclusion criteria were the use of silver-based dressing in children under 1 year of age. Outcomes of interest were complications or adverse events attributed to silver-based dressings and elevated serum silver levels. A total of 599 sources were identified through the search strategy, with 110 included for review. Complications were described in 31 sources, with the most frequent being wound infection. No cases of argyria, kernicterus, or methemoglobinemia were reported. Six sources documented elevated serum silver levels in infants but none reported adverse events related to this. On the basis of current evidence, we suggest reserving silver dressings in infants under 1 for wounds that are at high risk of infection. Wound area and duration of treatment should be considered when assessing the risk of systemic absorption of silver. Standardized data collection and recording of complications and adverse events is recommended to better inform future clinical decision-making.
Linking transcriptome and morphology in bone cells at cellular resolution with generative AI
Authors: Lu Lu , Ono Noriaki , Welch Joshua D
Published: September 2024

Recent advancements in deep learning (DL) have revolutionized the capability of artificial intelligence (AI) by enabling the analysis of large-scale, complex datasets that are difficult for humans to interpret. However, large amounts of high-quality data are required to train such generative AI models successfully. With the rapid commercialization of single-cell sequencing and spatial transcriptomics platforms, the field is increasingly producing large-scale datasets such as histological images, single-cell molecular data, and spatial transcriptomic data. These molecular and morphological datasets parallel the multimodal text and image data used to train highly successful generative AI models for natural language processing and computer vision. Thus, these emerging data types offer great potential to train generative AI models that uncover intricate biological processes of bone cells at a cellular level. In this Perspective, we summarize the progress and prospects of generative AI applied to these datasets and their potential applications to bone research. In particular, we highlight three AI applications: predicting cell differentiation dynamics, linking molecular and morphological features, and predicting cellular responses to perturbations. To make generative AI models beneficial for bone research, important issues, such as technical biases in bone single-cell datasets, lack of profiling of important bone cell types, and lack of spatial information, needs to be addressed. Realizing the potential of generative AI for bone biology will also likely require generating large-scale, high-quality cellular-resolution spatial transcriptomics datasets, improving the sensitivity of current spatial transcriptomics datasets, and thorough experimental validation of model predictions.
Testing for heterogeneous rates of discrete character evolution on phylogenies
Authors: Revell Liam J , Schliep Klaus P , Mahler D Luke , Ingram Travis
Published: September 2024

Many hypotheses in the field of phylogenetic comparative biology involve specific changes in the rate or process of trait evolution. This is particularly true of approaches designed to connect macroevolutionary pattern to microevolutionary process. We present a method to test whether the rate of evolution of a discrete character has changed in one or more clades, lineages, or time periods. This method differs from other related approaches (such as the “covarion” model) in that the “regimes” in which the rate or process is postulated to have changed are specified a priori by the user, rather than inferred from the data. Similarly, it differs from methods designed to model a correlation between two binary traits in that the regimes mapped onto the tree are fixed. We apply our method to investigate the rate of dewlap colour and/or caudal vertebra number evolution in Caribbean and mainland clades of the diverse lizard genus Anolis. We find little evidence to support any difference in the evolutionary process between mainland and island evolution for either character. We also examine the statistical properties of the method more generally and show that it has acceptable type I error, parameter estimation, and power. Finally, we discuss some general issues of frequentist hypothesis testing and model adequacy, as well as the relationship of our method to existing models of heterogeneity in the rate of discrete character evolution on phylogenies.
Interferon lambda signaling in neutrophils enhances the pathogenesis of Bordetella pertussis infection
Authors: Kumar Amit , Johnson Da’Kuawn , Bukowski Alicia , Noto Michael J , Carbonetti Nicholas H
Published: September 2024

Interferon lambda plays diverse roles in bacterial infections. Previously, we showed that interferon lambda is induced in the lungs of Bordetella pertussis-infected adult mice and exacerbates inflammation. Here, we report that mice lacking the interferon lambda receptor 1 specifically on neutrophils (MRP8creIFNLR1fl/fl mice) exhibit reduced lung bacterial load and inflammation compared to wild-type mice during B. pertussis infection. In B. pertussis-infected wild-type mice, lung type I and III IFN responses were higher than in MRP8creIFNLR1fl/fl mice, correlating with increased lung inflammatory pathology. There was an increased proportion of interferon gamma-producing neutrophils in the lungs of MRP8creIFNLR1fl/fl mice compared to wild-type mice. IFNLR1−/− neutrophils incubated with B. pertussis exhibited higher killing compared to wild-type neutrophils. Treatment of wild-type neutrophils with interferon lambda further decreased their bacterial killing capacity and treatment of wild-type mice with interferon lambda increased lung bacterial loads. Contributing to the differential killing, we found that IFNLR1−/− neutrophils exhibit higher levels of reactive oxygen species, myeloperoxidase, matrix metalloproteinase-9 activity, neutrophil extracellular traps, and interferon gamma secretion than wild-type neutrophils, and inhibiting NADPH oxidase inhibited bacterial killing in IFNLR1−/− neutrophils. B. pertussis-induced interferon lambda secretion and IFNLR1 gene expression in mouse and human neutrophils and this was dependent on the bacterial virulence protein pertussis toxin. Pertussis toxin enhanced bacterial loads in wild type but not in MRP8creIFNLR1fl/fl or IFNLR1−/− mice. Thus, pertussis toxin disrupts neutrophil function by enhancing type III IFN signaling, which prevents neutrophils from effectively clearing B. pertussis during infection, leading to higher bacterial loads and exacerbation of lung inflammation.
Analysis of the effect of nonlocal factors on the vibration of nanobeams
Authors: Wang Guobing , Wang Hui , Li Chunjiang , Zhang Dehong , Zeng Minjun
Published: September 2024

Currently, the Euler–Bernoulli beam nonlocal theory does not fully consider the effects of foundation deformation and axial force on the beams, and cannot accurately reflect the real mechanical properties of nanobeams. The primary objective of this study is to introduce a novel computational method designed for an enhanced characterization of the vibrational behavior of nanobeams. Initially, this method incorporates the influence of foundation deformation on beam bending, accounts for the effects of axial forces, integrates Eringen's nonlocal theory and establishes a modified Euler–Bernoulli beam theory model for the first time, accompanied by a degradation validation of the model. Subsequently, the Laplace transform and Hasselman's complex mode synthesis method are utilized to solve the model, providing the first derivation of the state-space transfer function for the nanobeam vibration model based on the modified Euler–Bernoulli beam theory. Lastly, the study elucidates the impact of nonlocal factors and various parameters on the vibration characteristics of nanobeams. The results show that the order n increases, and the peak frequency value moves in the direction where the nonlocal factor tends to zero. At the same order, the beam length increases, and the peak frequency moves in the direction of increasing nonlocal factor. The modified geometric parameters and the foundation beam stiffness parameters have a greater effect on the peak of the beam's vibration mode in the higher order case and a lesser effect in the lower order case. The larger the nonlocal factor, the larger the peak of the vibration mode.
What should we be studying? Research priorities according to women and gender-diverse individuals with sexual interest/arousal disorder and their partners
Authors: Shimizu Justin P K , Bergeron Sophie , Schwenck Gracielle C , Huberman Jackie S , Rosen Natalie O
Published: September 2024

Background

Sexual interest/arousal disorder (SIAD) is one of the most common sexual problems for women. In clinical research, there are often misalignments between the research priorities of patients and researchers, which can negatively impact care, and gender-diverse individuals are often excluded from research. Inclusion of patient perspectives when establishing research priorities may help to reduce these gaps; however, the research priorities of couples coping with SIAD remain unclear.

Aim

Identify the research priorities of women and gender-diverse individuals with SIAD and their partners.

Methods

In an online survey, couples coping with SIAD provided consent and responded to an open-ended question asking them to list the top 3 things they think are important for researchers to focus on related to couples coping with low sexual desire. A team-based content analysis was conducted to identify themes and their frequency of endorsement.

Outcomes

An author-developed open-ended question.

Results

Analysis of 1279 responses (n = 667 from women and gender-diverse individuals with SIAD, n = 612 from partners) resulted in our identification of 6 main themes: general causes, general treatment and coping, biophysiological, relationship, psychological, and environmental/contextual. Additionally, we identified 4 sub-themes within each of the latter 4 main themes: general, cause, treatment, and impact. For women and gender-diverse individuals with SIAD, their partners, and specifically gender-diverse participants, the 3 most endorsed themes were psychological general factors (24.3%, 21.2%, 24.3%; eg, stress and the link between SIAD and anxiety), relationship general factors (15.7%, 13.2%, 18.6%; eg, relationship length and communication on sexual desire), and biophysiological general factors (12.3%, 12.4%, 14.3%; eg, research on medications and hormones).

Clinical Implications

Clinical researchers should consider the research priorities of couples coping with SIAD to ensure their work aligns with the needs of the affected population.

Strengths and Limitations

This study is the first to identify the research priorities of both women and gender-diverse individuals with SIAD and their partners. Most participants identified as heterosexual, North American, and of middle to high socioeconomic status; results may not generalize. Responses were sometimes brief and/or vague; interpretation of these responses was therefore limited and may have required more contextual information.

Conclusion

Findings suggest that women and gender-diverse individuals with SIAD, their partners, and gender-diverse participants have similar research priorities that are consistent with a biopsychosocial approach to research. Heterogeneity of responses across themes supports a multidisciplinary, patient-oriented approach to SIAD research.
The impact of Marfan syndrome and Ehlers-Danlos syndrome on the risk of penile fracture in patients between 18 and 45 years
Authors: Kolanukuduru Kaushik P , Mandel Asher L , Simhal Rishabh K , Sholklapper Tamir N , Sun Kelly , Poluch Maria , Wang Kerith R , Shah Yash B , Chung Paul H
Published: September 2024

Background

Despite knowledge of the pathophysiology and clinical complications of connective tissue diseases (CTD), little is known regarding their impact on men’s sexual health disorders.

Aim

To investigate the prevalence of penile fracture (PF) in patients with Ehlers-Danlos Syndrome (EDS) and Marfan syndrome (MFS) in comparison with disease-free controls between 18 and 45 years of age.

Methods

A multicenter, international, electronic health record network (TriNetX) was queried to identify adult male patients (between 18 and 45 years) with or without EDS and MFS between 1993 and 2023 using ICD-10 codes. The prevalence of PF was compared between patients with and without the diseases of interest. Prevalence ratios (PR) were generated with 95% confidence intervals.

Outcome

Prevalence of PF in patients with EDS and MFS when compared to disease-free controls.

Results

The number of patients with EDS, MFS, and control groups was 8060, 8642, and 20 184 547, respectively, with a mean age of 27.8 ± 7.58, 28.6 ± 7.4, and 31.6 ± 8.04 years. Men with EDS had a higher prevalence of PF (PR 30.18, 95% CI [17.08–53.19]; P < 0.0001). Similarly, men with MFS had a higher prevalence of PF (PR 23.4, 95% CI [12.6–43.7]; P < 0.0001).

Clinical implications

This study demonstrates an association between CTD and men’s sexual health disorders. It may be important to counsel such men about the risks of PF.

Strengths and Limitations

This is the largest study to date to demonstrate an association between CTD and men’s sexual health disorders. While the large sample sizes in this study contribute to the robustness of the findings, the study is limited by the use of a claims-based dataset, which does not provide further details about disease course and complications, and the use of a univariate analysis only.

Conclusions

Patients with EDS and MFS are possibly at an elevated risk for PF. Due to the limitations of the TriNetX database, the analysis was limited to a univariate one, thus limiting the ability to control for confounders and limiting the generalizability of these findings. Further prospective research is needed to corroborate these findings.
Mitogen-activated protein kinase-mediated regulation of plant specialized metabolism
Authors: Zhou Yan , Singh Sanjay Kumar , Patra Barunava , Liu Yongliang , Pattanaik Sitakanta , Yuan Ling
Published: September 2024

Post-transcriptional and post-translational modification of transcription factors (TFs) and pathway enzymes significantly affect the stress-stimulated biosynthesis of specialized metabolites (SMs). Protein phosphorylation is one of the conserved and ancient mechanisms that critically influences many biological processes including specialized metabolism. The phosphorylation of TFs and enzymes by protein kinases (PKs), especially the mitogen-activated protein kinases (MAPKs), is well studied in plants. While the roles of MAPKs in plant growth and development, phytohormone signaling, and immunity are well elucidated, significant recent advances have also been made in understanding the involvement of MAPKs in specialized metabolism. However, a comprehensive review highlighting the significant progress in the past several years is notably missing. This review focuses on MAPK-mediated regulation of several important SMs, including phenylpropanoids (flavonoids and lignin), terpenoids (artemisinin and other terpenoids), alkaloids (terpenoid indole alkaloids and nicotine), and other nitrogen- and sulfur-containing SMs (camalexin and indole glucosinolates). In addition to MAPKs, other PKs also regulate SM biosynthesis. For comparison, we briefly discuss the regulation by other PKs, such as sucrose non-fermenting-1 (SNF)-related protein kinases (SnRKs) and calcium-dependent protein kinases (CPKs). Furthermore, we provide future perspectives in this active area of research.
Identifying Improvements in Treating Extremity Musculoskeletal Injuries During Prolonged Care
Authors: Johnson W Brett , Perry Antuione D , Flores Garrett , Pierrie Sarah N , Alderete Joseph F , Allen Paul , Wilson Jonathan , King David , Childers W Lee
Published: September 2024

Introduction

In prolonged care scenarios, where medical evacuations are significantly delayed, the treatment and transport of casualties with extremity musculoskeletal injuries will drain combat units’ human resources. Developing enhanced splinting techniques to restore casualty mobility and function can alleviate this drain. To guide this development, a panel of tactical combat and wilderness medicine experts was assembled to determine which extremity musculoskeletal injuries had the greatest impact on unit capabilities, and the materials available for splinting these injuries.

Information Gathering

Unstructured consultations with panel members yielded preliminary lists of injuries and materials. These lists were consolidated and redistributed to panel members for final evaluation where they ranked the injuries based on frequency and human resource cost and assessed the accessibility of materials. Responses for the final evaluation were statistically analyzed using Wilcoxon rank-sum tests and Placket Luce models.

Lessons Learned

Aggregated responses indicated that panel members thought that knee and ankle ligamentous injuries and radial head fractures were the most frequently occurring injuries, although closed distal femoral fractures, below knee amputations, and open tibia fractures would require the most demand for injury care. Assessing the combined impact of frequency and human resource cost indicated that knee and ankle ligamentous injuries and closed tibia fractures had the greatest impact on unit readiness. Responses also indicated that a variety of materials would be available for applying or improvising splints.

Conclusion

Although the combined impact of knee and ankle ligamentous injuries were ranked the highest, limitations in relative rankings and the existence of effective low-cost treatments for these injuries suggest that greater gains in unit effectiveness would come from focusing on developing solutions for fractures with higher human resource cost, such as leg and arm fractures. This information can be used to develop enhanced splints that can preserve unit readiness in the field.
A Clean You Can Trust: Using an Evidence-Based Bundle to Transform Point-of-Use Treatment for Reusable Medical Devices at a Military Treatment Facility
Authors: Atwood Bethany I , Eberhardt Gina L , Smith Joshua D , Lawton Danielle N , Macdonald Erin M , Romito Kenneth
Published: September 2024

Introduction

Throughout surgical and invasive procedures, reusable instruments and flexible endoscopes become soiled with organic and inorganic materials. When these substances are permitted to dry, a matrix of microbial cells, called biofilm, forms on the surface of devices, irreversibly binding and subsequently impeding the disinfection and sterilization process. To prevent biofilm formation from occurring, devices must be continuously flushed and wiped with water throughout the procedure and at the end of the case. This process, known as point-of-use treatment (POUT), is the critical first step in the decontamination of medical devices. Poor compliance with POUT can increase patient morbidity and mortality and result in failing hospital accreditation.

Materials and Methods

An interdisciplinary team used the Plan-Do-Study-Act (PDSA) to develop and implement an audit assessing 29 evidence-based criteria for POUT treatment. Each PDSA cycle supported evidence-based opportunities addressing feedback, workflow analysis, policy development, competency assessment creation, training module development, and infection prevention grand rounds. Four audits were performed over ten months to achieve improved organizational POUT compliance.

Results

Implementing recurrent PDSA cycles that included audits with feedback led to an evidence-based bundle of policies, competencies, and training for 34 different clinical areas. These interventions resulted in a 26% compliance increase (66% to 92%). Program-specific improvements included flexible endoscopes (+4%) and reusable instruments (+20%).

Conclusions

Multimodal evidence-based initiatives to improve compliance with workflow processes is a translatable POUT evidence-based practice project for similar Defense Health Agengy facilities. Workflow processes can be vetted and distributed using interdisciplinary teams to ensure viability, sustainability, and conformity with organizational requirements, resulting in a more ready force.
AHKASH: a new Hybrid particle-in-cell code for simulations of astrophysical collisionless plasma
Authors: Achikanath Chirakkara Radhika , Federrath Christoph , Seta Amit
Published: September 2024

We introduce Astrophysical Hybrid-Kinetic simulations with the flash code ($\tt {AHKASH}$) – a new Hybrid particle-in-cell (PIC) code developed within the framework of the multiphysics code flash. The new code uses a second-order accurate Boris integrator and a predictor–predictor–corrector algorithm for advancing the Hybrid-kinetic equations, using the constraint transport method to ensure that magnetic fields are divergence-free. The code supports various interpolation schemes between the particles and grid cells, with post-interpolation smoothing to reduce finite particle noise. We further implement a $\delta f$ method to study instabilities in weakly collisional plasmas. The new code is tested on standard physical problems such as the motion of charged particles in uniform and spatially varying magnetic fields, the propagation of Alfvén and whistler waves, and Landau damping of ion acoustic waves. We test different interpolation kernels and demonstrate the necessity of performing post-interpolation smoothing. We couple the turbgen turbulence driving module to the new Hybrid PIC code, allowing us to test the code on the highly complex physical problem of the turbulent dynamo. To investigate steady-state turbulence with a fixed sonic Mach number, it is important to maintain isothermal plasma conditions. Therefore, we introduce a novel cooling method for Hybrid PIC codes and provide tests and calibrations of this method to keep the plasma isothermal. We describe and test the ‘hybrid precision’ method, which significantly reduces (by a factor $\sim 1.5$) the computational cost, without compromising the accuracy of the numerical solutions. Finally, we test the parallel scalability of the new code, showing excellent scaling up to 10,000 cores.
Evolutionary Innovations in Conserved Regulatory Elements Associate With Developmental Genes in Mammals
Authors: Uebbing Severin , Kocher Acadia A , Baumgartner Marybeth , Ji Yu , Bai Suxia , Xing Xiaojun , Nottoli Timothy , Noonan James P
Published: September 2024

Transcriptional enhancers orchestrate cell type- and time point-specific gene expression programs. Genetic variation within enhancer sequences is an important contributor to phenotypic variation including evolutionary adaptations and human disease. Certain genes and pathways may be more prone to regulatory evolution than others, with different patterns across diverse organisms, but whether such patterns exist has not been investigated at a sufficient scale. To address this question, we identified signatures of accelerated sequence evolution in conserved enhancer elements throughout the mammalian phylogeny at an unprecedented scale. While different genes and pathways were enriched for regulatory evolution in different parts of the tree, we found a striking overall pattern of pleiotropic genes involved in gene regulatory and developmental processes being enriched for accelerated enhancer evolution. These genes were connected to more enhancers than other genes, which was the basis for having an increased amount of sequence acceleration over all their enhancers combined. We provide evidence that sequence acceleration is associated with turnover of regulatory function. Detailed study of one acceleration event in an enhancer of HES1 revealed that sequence evolution led to a new activity domain in the developing limb that emerged concurrently with the evolution of digit reduction in hoofed mammals. Our results provide evidence that enhancer evolution has been a frequent contributor to regulatory innovation at conserved developmental signaling genes in mammals.
Corpus Studies, Sonata Typology, and the Nineteenth-Century Violin Concerto: Viotti, Saint-Saëns, and the Challenge of Recapitulatory Compression
Authors: Horton Julian , Smith Peter H
Published: September 2024

A corpus study of first-movement form in the nineteenth-century violin concerto, encompassing works from Viotti to Elgar, addresses: the New Formenlehre’s lack of attention to the genre, the pitfalls of formal theory’s focus on canonical Austro-German repertoire; and the question of how concepts derived from late eighteenth-century practice need to adapt to nineteenth-century evolutions. In some geographic subcategories of the corpus, recapitulatory compression is as prevalent as the presumably normative tonic return of P and S. Composers explore multiple alternatives: bypassing recapitulation of either of these zones, merging them, or recapitulating neither in a truncated form that flows into the slow movement. These practices unsettle the tendency to treat the Mozartian type 5 form as a yardstick, reveal a heretofore unrecognized type 2 lineage originating in the eighteenth century and stretching across the nineteenth, and expose the shortcomings of over-reliance on canonical repertoire. Two case studies of Viotti and Saint-Saëns highlight related practices across the corpus’s long chronological span and counterbalance the corpus’s bird’s eye view with attention to the aesthetically compelling formal complexities revealed by close reading of individual compositions.