bluuebunny/crossref_metadata_2025 huggingface dataset:
To live or let die? Epigenetic adaptations to climate change—a review
Authors: Zetzsche Jonas , Fallet Manon
Published: August 2024

Anthropogenic activities are responsible for a wide array of environmental disturbances that threaten biodiversity. Climate change, encompassing temperature increases, ocean acidification, increased salinity, droughts, and floods caused by frequent extreme weather events, represents one of the most significant environmental alterations. These drastic challenges pose ecological constraints, with over a million species expected to disappear in the coming years. Therefore, organisms must adapt or face potential extinctions. Adaptations can occur not only through genetic changes but also through non-genetic mechanisms, which often confer faster acclimatization and wider variability ranges than their genetic counterparts. Among these non-genetic mechanisms are epigenetics defined as the study of molecules and mechanisms that can perpetuate alternative gene activity states in the context of the same DNA sequence. Epigenetics has received increased attention in the past decades, as epigenetic mechanisms are sensitive to a wide array of environmental cues, and epimutations spread faster through populations than genetic mutations. Epimutations can be neutral, deleterious, or adaptative and can be transmitted to subsequent generations, making them crucial factors in both long- and short-term responses to environmental fluctuations, such as climate change. In this review, we compile existing evidence of epigenetic involvement in acclimatization and adaptation to climate change and discuss derived perspectives and remaining challenges in the field of environmental epigenetics.

Graphical Abstract
Desmoplakin cardiomyopathy: case report
Authors: Helal Ayman , Alama Mohamed , Ali Wael , Farooq Mohsen
Published: August 2024

Background

Desmoplakin (DSP) cardiomyopathy is a distinct form of cardiomyopathy characterized by frequent left ventricular involvement with extensive fibrosis, high arrhythmic risk, and episodes of acute myocardial injury.

Case summary

We are reporting diagnosis and management of a rare case of DSP cardiomyopathy. A patient in his 70s was investigated for mild shortness of breath, recurrent chest infection, and multiple ventricular ectopic. His echocardiogram showed impaired systolic function and found to have 53% ectopic burden with run of non-sustained ventricular tachycardia on 24 h electrocardiogram. Cardiac magnetic resonance imaging showed findings highly suggestive of DSP cardiomyopathy. High-resolution computed tomography chest suggested connective tissue–related interstitial lung disease. The diagnosis of DSP cardiomyopathy was confirmed by genetic testing that demonstrated mutation in DSP protein. The patient had implantable cardioverter-defibrillator implantation for primary prevention.

Discussion

Implantable cardioverter-defibrillator implantation should be considered with left ventricular ejection fraction thresholds >35%, particularly in the presence of additional risk factors.
Colchicine for cardiovascular and limb risk reduction in Medicare beneficiaries with peripheral artery disease: emulation of target trials
Authors: Heindel Patrick , Fitzgibbon James J , Secemsky Eric , Bhatt Deepak L , Al-Omran Mohammed , Verma Subodh , Almaghlouth Ibrahim A , Madenci Arin , Hussain Mohamad A
Published: August 2024

Aims

Recent evidence from randomized trials demonstrates that colchicine can reduce the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease. Colchicine’s effect on lower-extremity peripheral artery disease (PAD) is not known.

Methods and results

To make inferences about the real-world effectiveness of colchicine in PAD, we emulated two target trials leveraging the variable prescribing practice of adding colchicine vs. a non-steroidal anti-inflammatory drug (NSAID) to urate-lowering therapy in patients with gout and PAD. Emulated Trial 1 compared colchicine initiators with NSAID initiators. Emulated Trial 2 compared long-term (indefinite) and short-term (3 months) treatment strategies after initiating colchicine. Eligible individuals were those continuously enrolled in Medicare receiving care at a multicentre academic health system between July 2007 and December 2019. The primary outcome for both trials was a 2 year composite of major adverse limb events (MALE), MACE, and all-cause mortality. Secondary outcomes included MALE and death, MACE and death, and individual components of the primary outcome. Inverse probability weighting was used to adjust for confounding. Percentile-based 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. A total of 1820 eligible patients were included; the mean age was 77 years [standard deviation (SD) 7], 32% were female, and 9% were non-White. The mean (SD) duration of colchicine and NSAID therapy was 247 (345) and 137 (237) days, respectively. In the emulation of Trial 1, the risk of the primary composite outcome of MALE, MACE, and death at 2 years was 29.9% (95% CI 27.2%, 32.3%) in the colchicine group and 31.5% (28.3%, 34.6%) in the NSAID group, with a risk difference of −1.7% (95% CI −6.5%, 3.1%) and a risk ratio of 0.95 (95% CI 0.83, 1.07). Similar findings were noted in the emulation of Trial 2, with a risk of the primary composite outcome at 2 years of 30.7% (95% CI 23.7%, 38.1%) in the long-term colchicine group and 33.4% (95% CI 29.4%, 37.7%) in the short-term group, with a risk difference of −2.7% (95% CI −10.3%, 5.4%) and risk ratio of 0.92 (95% CI 0.70, 1.16).

Conclusion

In a real-world sample of patients with PAD and gout, estimates of the effect of colchicine were consistent across two analyses and provided no conclusive evidence that colchicine decreased the risk of adverse cardiovascular or limb events and death. The cardiovascular and limb benefits of colchicine in older, comorbid populations with PAD and advanced systematic atherosclerosis remain uncertain.
Development and Validation of Physical Disability Index and Mental Disability Index and Their Associations With Falls Among Older Adults
Authors: Zhang Xuxi , Sun Xinying , Yin Pengbin , Zhang Licheng , Tang Peifu , Zeng Yi
Published: August 2024

Background

To enhance the precision of measuring, analyzing, and forecasting care needs for older adults with physical and/or mental disabilities, we developed the Physical Disability Index (PDI) and Mental Disability Index (MDI). Furthermore, we evaluated the reliability and validity of the PDI and MDI. Additionally, we investigate their associations with falls to further indicate the predictive validity.

Methods

A total of 11 621 older adults (53.1% women; mean age = 83.2; SD = 10.8) from 23 provinces in China were investigated in 2017–2018 to assess the reliability and validity of the PDI and MDI among older adults aged 65 to 105. Among which, 6 071 older adults with both baseline (2017–2018) and follow-up (2021) data were included in analyses to evaluate associations between the baseline health status determined by PDI and MDI and the number and severity of falls at baseline and follow-up. Cronbach’s alpha was used to determine internal consistency. The convergent and divergent validity, known-group validity and concurrent validity were assessed. Multinomial logistic regression models were utilized to assess associations.

Results

We found satisfactory internal consistency (Cronbach’s alpha ≥ 0.70) of the PDI and MDI in the total sample and sex-specific subgroups. Our results support the convergent and divergent validity, known-group validity, and concurrent validity of the PDI and MDI. We also found baseline physical disability and comorbid physical and mental disability are associated with a higher risk of baseline and follow-up falls.

Conclusions

The PDI and MDI are reliable and valid instruments to assess physical and mental disability status among older adults, respectively.
New Law Responding to Imitations of Designs that Intersect Real and Virtual Space: Amendment of the Unfair Competition Prevention Act in Japan
Authors: Komada Yasuto
Published: August 2024

Digital items that have the appearance of real utilitarian products are often tied to NFTs (Non-Fungible Tokens) in the virtual space known as the metaverse, and sold as goods. The designs of real utilitarian products are increasingly being converted into the designs of such NFT goods without the permission of their developers. In order to deal with these imitations, which intersect the real and the virtual worlds, the Japanese legislator decided to utilize the existing provision for the protection of forms of goods in the unfair competition prevention law (UCPA 1993). The law was amended in June 2023 to newly define ‘the act of offering through telecommunication line’ goods that imitate the form of another person’s goods as an act of unfair competition.

Copyright protection under Japanese case law has rarely been granted to designs of utilitarian products, and under Japanese design law the product design is identified not only by its shape but also by its product type. The protection of image designs is almost exclusively limited to specific images unrelated to the NFT goods. However, the revised provision of UCPA 1993 has also been generally interpreted as the provision prohibiting the imitation of designs between homogeneous products. The amendment effectively negates this interpretation.

This paper reveals the impact on the existing interpretation of the relevant provision of UCPA 1993 and the issues arising from other legal provisions with respect to such imitations.
Genotype-associated core bacteria enhance host resistance against kiwifruit bacterial canker
Authors: Fu Min , Chen Yunhe , Liu Yong-Xin , Chang Xiaoxi , Zhang Lei , Yang Xinyi , Li Li , Zhang Lixin
Published: August 2024

Both the phyllosphere and rhizosphere are inhabited by different kinds of microorganisms that are closely related to plant growth and health. However, it is not clear whether disease-resistant cultivars shape the microbiome to facilitate disease resistance. In this study, significant differences were found in the aboveground and belowground bacterial communities of disease-resistant and disease-susceptible cultivars grown in the same kiwifruit orchard. The phyllosphere of the resistant cultivar ‘Wanjin’ showed greater enrichment of Pseudomonas spp. and Sphingomonas spp. than the susceptible cultivar ‘Donghong’. The rhizosphere microbes of ‘Wanjin’ were less affected by field location, with significantly greater bacterial abundance than those of ‘Donghong’ and more bacteria with potential biocontrol properties. Pseudomonas syringae pv. actinidiae (Psa) infection significantly affected the microbiome of the phyllosphere of kiwifruit plants, especially that of ‘Donghong’. Resistant and susceptible kiwifruit cultivars exhibit distinct beneficial microbial recruitment strategies under Psa challenge. The phyllosphere of ‘Donghong’ in Jinzhai was enriched with Sphingomonas spp. and Pantoea spp. under Psa infection, while the rhizosphere of ‘Wanjin’ was enriched with Sphingomonas spp. and Novosphingobium spp. We further identified five key biomarkers within the microbial community associated with Psa infection. Inoculation experiments showed that Lysobacter sp. R34, Stenotrophomonas sp. R31, Pseudomonas sp. R10 and RS54, which were isolated from belowground compartments of ‘Wanjin’, could positively affect plant performance under Psa challenge. The combination use of Pseudomonas sp. R10 and Stenotrophomonas sp. R31 significantly improve the management of kiwifruit canker. Our findings provided novel insights into soil–microbe–plant interactions and the role of microbes in plant disease resistance and susceptibility.
Generalized kernel distance covariance in high dimensions: non-null CLTs and power universality
Authors: Han Qiyang , Shen Yandi
Published: August 2024

Distance covariance is a popular dependence measure for two random vectors $X$ and $Y$ of possibly different dimensions and types. Recent years have witnessed concentrated efforts in the literature to understand the distributional properties of the sample distance covariance in a high-dimensional setting, with an exclusive emphasis on the null case that $X$ and $Y$ are independent. This paper derives the first non-null central limit theorem for the sample distance covariance, and the more general sample (Hilbert–Schmidt) kernel distance covariance in high dimensions, in the distributional class of $(X,Y)$ with a separable covariance structure. The new non-null central limit theorem yields an asymptotically exact first-order power formula for the widely used generalized kernel distance correlation test of independence between $X$ and $Y$. The power formula in particular unveils an interesting universality phenomenon: the power of the generalized kernel distance correlation test is completely determined by $n\cdot \operatorname{dCor}^{2}(X,Y)/\sqrt{2}$ in the high-dimensional limit, regardless of a wide range of choices of the kernels and bandwidth parameters. Furthermore, this separation rate is also shown to be optimal in a minimax sense. The key step in the proof of the non-null central limit theorem is a precise expansion of the mean and variance of the sample distance covariance in high dimensions, which shows, among other things, that the non-null Gaussian approximation of the sample distance covariance involves a rather subtle interplay between the dimension-to-sample ratio and the dependence between $X$ and $Y$.
Rank Zero Segre Integrals on Hilbert Schemes of Points on Surfaces
Authors: Yuan Yao
Published: August 2024

The generating function of the Segre integrals on Hilbert schemes of points on a surface $X$ can be determined by five universal series $A_{0}(z)$, $A_{1}(z)$, $A_{2}(z)$, $A_{3}(z)$, $A_{4}(z)$, due to the result of Ellingsrud–Göttsche–Lehn. These five series do not depend on the surface $X$ and depend on the element $\alpha \in K(X)$, to which the Segre integrals are associated, only through the rank. Marian–Oprea–Pandharipande have determined $A_{0}(z),A_{1}(z),A_{2}(z)$ for all ranks. For rank 0, it is easy to see $A_{4}(z)=1$. Marian–Oprea–Pandharipande also conjectured that $A_{3}(z)=A_{0}(z)A_{1}(z)$ for rank 0. We prove this conjecture by showing that when $X$ is the projective plan, the Segre integrals associated to the structure sheaf of a curve in the anti-canoncial class are all zero. Hence, the rank zero Segre integrals on the Hilbert schemes of points for all surfaces are determined.
Disguise or surprise: spider antipredator adaptations as a function of the architecture of their webs
Authors: Haberkern Andrea M , Boles Jessica C , Zhou Yi Lin , Camacho Luis F , Brescovit Antonio D , Avilés Leticia
Published: August 2024

Animals exhibit a variety of strategies to avoid predation; spiders are no exception. We explored whether web-building spiders that differ in the architecture of their webs exhibit morphologies or behaviors suggestive of antipredator strategies that trade-off with the degree of protection offered by their webs. Spiders build webs of 3 types: the more protected tangles and sheet-and-tangles, which are three-dimensional (3D), and the more exposed orbs, which are two-dimensional (2D), both with or without a refuge. We hypothesize that spiders whose webs offer greater protection—a 3D architecture or a refuge—will be less likely to be armored or brightly colored when compared to spiders without these protections. We collected data on 446 spiders and their webs in 2 lowland tropical rainforest sites. We show that 2D web builders with no refuges tended to be brightly colored (background contrasting) and spiny (spiky), whereas those with refuges tended to blend against the background of their refuges. 3D web builders, on the other hand, were neither cryptic nor brightly colored nor armored but were more likely to drop out of the web upon simulated predator contact. These results support the hypothesis that web-building spiders tend to be protected either through the architecture of their webs or their morphology and behavior, suggesting a trade-off between different types of antipredator strategies.
Mass Attitudes about International Trade Agreements: Positive Messages and the Trans-Pacific Partnership
Authors: Bearce David H , Park Seungbin
Published: August 2024

From the understanding that the mass public knows little about the benefits of international trade agreements but nonetheless opposes them with opposition representing a problem for domestic ratification, this research note explores if and what messages about the Trans-Pacific Partnership might increase popular support. The experimental results show that providing more background information alone does not increase support, but adding an economic message about how this agreement could lower prices or a security message about how it would help the United States counter China increases support. The economic message also encourages respondents to write a statement to their Senators urging them to vote for ratification. These positive effects appear even within groups that are more opposed, namely less educated citizens and Republicans. Our results address important questions about the formation of trade policy preferences, showing they can be shifted in directions contrary to one's egocentric interests and partisan predispositions.
Designing the Australian Cancer Atlas: visualizing geostatistical model uncertainty for multiple audiences
Authors: Goodwin Sarah , Saunders Thom , Aitken Joanne , Baade Peter , Chandrasiri Upeksha , Cook Dianne , Cramb Susanna , Duncan Earl , Kobakian Stephanie , Roberts Jessie , Mengersen Kerrie
Published: August 2024

Objective

The Australian Cancer Atlas (ACA) aims to provide small-area estimates of cancer incidence and survival in Australia to help identify and address geographical health disparities. We report on the 21-month user-centered design study to visualize the data, in particular, the visualization of the estimate uncertainty for multiple audiences.

Materials and Methods

The preliminary phases included a scoping study, literature review, and target audience focus groups. Several methods were used to reach the wide target audience. The design and development stage included digital prototyping in parallel with Bayesian model development. Feedback was sought from multiple workshops, audience focus groups, and regular meetings throughout with an expert external advisory group.

Results

The initial scoping identified 4 target audience groups: the general public, researchers, health practitioners, and policy makers. These target groups were consulted throughout the project to ensure the developed model and uncertainty visualizations were effective for communication. In this paper, we detail ACA features and design iterations, including the 3 complementary ways in which uncertainty is communicated: the wave plot, the v-plot, and color transparency.

Discussion

We reflect on the methods, design iterations, decision-making process, and document lessons learned for future atlases.

Conclusion

The ACA has been hugely successful since launching in 2018. It has received over 62 000 individual users from over 100 countries and across all target audiences. It has been replicated in other countries and the second version of the ACA was launched in May 2024. This paper provides rich documentation for future projects.
Empowering the biomedical research community: Innovative SAS deployment on the All of Us Researcher Workbench
Authors: Humes Izabelle , Shyr Cathy , Dillon Moira , Liu Zhongjie , Peterson Jennifer , Jeor Chris St , Malkes Jacqueline , Master Hiral , Mapes Brandy , Azuine Romuladus , Mack Nakia , Abdelbary Bassent , Gamble-George Joyonna , Goldmann Emily , Cook Stephanie , Choupani Fatemeh , Baskir Rubin , McMaster Sydney , Lunt Chris , Watson Karriem , Lee Minnkyong , Schwartz Sophie , Munshi Ruchi , Glazer David , Banks Eric , Philippakis Anthony , Basford Melissa , Roden Dan , Harris Paul A
Published: August 2024

Objectives

The All of Us Research Program is a precision medicine initiative aimed at establishing a vast, diverse biomedical database accessible through a cloud-based data analysis platform, the Researcher Workbench (RW). Our goal was to empower the research community by co-designing the implementation of SAS in the RW alongside researchers to enable broader use of All of Us data.

Materials and Methods

Researchers from various fields and with different SAS experience levels participated in co-designing the SAS implementation through user experience interviews.

Results

Feedback and lessons learned from user testing informed the final design of the SAS application.

Discussion

The co-design approach is critical for reducing technical barriers, broadening All of Us data use, and enhancing the user experience for data analysis on the RW.

Conclusion

Our co-design approach successfully tailored the implementation of the SAS application to researchers' needs. This approach may inform future software implementations on the RW.
Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia
Authors: Dahir Kathryn M , Shannon Amy , Dunn Derek , Voegtli Walter , Dong Qunming , Hasan Jawad , Pradhan Rajendra , Pelto Ryan , Pan Wei-Jian
Published: August 2024

Hypophosphatasia (HPP) is a rare, inherited metabolic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). Efzimfotase alfa (ALXN1850) is a second-generation TNSALP enzyme replacement therapy in development for HPP. This first-in-human open-label, dose-escalating phase 1 trial evaluated efzimfotase alfa safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. Fifteen adults (5/cohort) with HPP received efzimfotase alfa in doses of 15 mg (cohort 1), 45 mg (cohort 2), or 90 mg (cohort 3) as one intravenous (i.v.) dose followed by 3 weekly subcutaneous (s.c.) doses. The primary objective was to assess safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics of ALP substrates known to be biomarkers of disease (inorganic pyrophosphate [PPi] and pyridoxal 5′-phosphate [PLP]) and immunogenicity. Treatment-emergent adverse events (TEAEs) occurred in 12 (80%) participants. Eight (53%) participants had injection site reactions (ISRs), observed after 10 of 41 (24%) s.c. injections. Most ISR TEAEs were mild and resolved within 1–2 d. Peak and total exposures of efzimfotase alfa increased in a greater-than-dose proportional manner over the range of 15–90 mg after i.v. and s.c. dosing. The arithmetic mean elimination half-life was approximately 6 d; absolute bioavailability was 28.6%–36.8% over the s.c. dose range of 15–90 mg. Dose-dependent reductions in plasma concentrations of PPi and PLP relative to baseline reached nadir in the first week after i.v. dosing and were sustained for 3–4 wk after the last s.c. dose. Four (27%) participants tested positive for antidrug antibodies (ADAs), 3 of whom were ADA positive before the first dose of efzimfotase alfa. ADAs had no apparent effect on efzimfotase alfa pharmacokinetics/pharmacodynamics. No participants had neutralizing antibodies. Efzimfotase alfa demonstrated acceptable safety, tolerability, and pharmacokinetic profiles and was associated with sustained reductions in biomarkers of disease in adults with HPP, supporting further evaluation in adult and pediatric patients.

Registration: ClinicalTrials.gov NCT04980248 (https://clinicaltrials.gov/study/NCT04980248).
Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine
Authors: Tchalla Essi Y I , Betadpur Anagha , Khalil Andrew Y , Bhalla Manmeet , Bou Ghanem Elsa N
Published: August 2024

Vaccine-mediated protection and susceptibility to Streptococcus pneumoniae (pneumococcus) infections are influenced by biological sex. The incidence of invasive pneumococcal disease remains higher in males compared to females even after the introduction of the pneumococcal conjugate vaccine. However, sex-based differences in the immune response to this conjugate vaccine remain unexplored. To investigate those differences, we vaccinated adult male and female mice with pneumococcal conjugate vaccine and assessed cellular and humoral immune responses. Compared to females, male mice displayed lower levels of T follicular helper cells, germinal center B cells, and plasmablasts, which are all required for antibody production following vaccination. This was linked to lower IgG and IgM levels against pneumococci and lower isotype switching to IgG3 in vaccinated males. Due to lower antibody levels, sera of vaccinated male mice had lower efficacy in several anti-pneumococcal functions, including neutralization of bacterial binding to pulmonary epithelial cells as well as direct cytotoxicity against S. pneumoniae. Importantly, while the vaccine was highly protective in females, vaccinated males succumbed to infection more readily and were more susceptible to both lung-localized infection and systemic spread following S. pneumoniae challenge. These findings identify sex-based differences in immune responses to pneumococcal conjugate vaccine that can inform future vaccine strategies.
Mesenchymal stem cell-derived exosomal microRNA-367-3p mitigates lower limb ischemia/reperfusion injury in mouse skeletal muscle via EZH2 targeting
Authors: Sun Huanhuan , Wang Jueqiong , Bi Wei , Zhang Feng , Zhang Kai , Tian Xitao , Gao Xiang , Zhang Yanrong
Published: August 2024

Objective

This study aimed to investigate the protective effect of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-exo) against lower limb ischemia/reperfusion (I/R) injury-induced pyroptosis in skeletal muscle.

Methods

A mouse model of lower limb I/R injury was utilized to assess the impact of BMSCs-exo, particularly when loaded with microRNA-367-3p (miR-367-3p), on pyroptosis. Histological examination, wet weight/dry weight ratio measurements, and luciferase assays were employed to elucidate the mechanisms involved.

Key findings

BMSCs-exo effectively suppressed pyroptosis in injured skeletal muscle tissue. Loading BMSCs-exo with miR-367-3p enhanced this protective effect by downregulating key pyroptosis-related proteins. Luciferase assays identified enhancer of zeste homolog 2 (EZH2) as a direct target of miR-367-3p in BMSCs-exo.

Conclusions

BMSCs-exo loaded with miR-367-3p safeguarded mouse skeletal muscle against pyroptosis-induced I/R injury by targeting EZH2. These findings offer valuable insights into potential therapeutic strategies for lower limb I/R injuries, emphasizing the therapeutic potential of BMSCs-exo in mitigating tissue damage caused by pyroptosis.
Protein kinase MeSnRK2.3 positively regulates starch biosynthesis by interacting with the transcription factor MebHLH68 in cassava
Authors: Li Ke , Li Yajun , Liu Chen , Li Mengtao , Bao Ruxue , Wang Haiyan , Zeng Changying , Zhou Xincheng , Chen Yinhua , Wang Wenquan , Chen Xin
Published: August 2024

Starch biosynthesis involves numerous enzymes and is a crucial metabolic activity in plant storage organs. Sucrose non-fermenting related protein kinase 2 (SnRK2) is an abscisic acid (ABA)-dependent kinase and a significant regulatory enzyme in the ABA signaling pathway. However, whether SnRK2 kinases regulate starch biosynthesis is unclear. In this study, we identified that MeSnRK2.3, encoding an ABA-dependent kinase, was highly expressed in the storage roots of cassava (Manihot esculenta) and was induced by ABA. Overexpression of MeSnRK2.3 in cassava significantly increased the starch content in the storage roots and promoted plant growth. MeSnRK2.3 was further found to interact with the cassava basic helix–loop–helix 68 (MebHLH68) transcription factor in vivo and in vitro. MebHLH68 directly bound to the promoters of sucrose synthase 1 (MeSUS1), granule-bound starch synthase I a (MeGBSSIa), and starch-branching enzyme 2.4 (MeSBE2.4), thereby up-regulating their transcriptional activities. Additionally, MebHLH68 negatively regulated the transcriptional activity of sucrose phosphate synthase B (MeSPSB). Moreover, MebHLH68 phosphorylated by MeSnRK2.3 up-regulated the transcription activity of MeSBE2.4. These findings demonstrated that the MeSnRK2.3–MebHLH68 module connects the ABA signaling pathway and starch biosynthesis in cassava, thereby providing direct evidence of ABA-mediated participation in the sucrose metabolism and starch biosynthesis pathways.
LEP rs7799039 and LEPR rs1137101 gene variants are not associated with clinical features in patients with metabolic syndrome in the Turkish population
Authors: Jabbarli Marjan , Senkal Naci , Tuncel Fatima Ceren , Oyaci Yasemin , Guzel Dirim Merve , Kose Murat , Pehlivan Sacide , Medetalibeyoglu Alpay
Published: August 2024

Objectives

Genetic predisposition plays a role in the etiology of metabolic syndrome (MetS), an important health problem worldwide. Leptin (LEP), produced by adipose tissue, plays a crucial role in the development of MetS. In this study, we evaluated the effects of LEP and LEP receptor (LEPR) variants on clinical findings and risk of developing MetS in the Turkish population.

Methods

A total of 320 patients were included in the study, of whom 150 were patients with MetS and 170 were healthy controls. DNA was extracted from blood samples. LEP rs7799039 and LEPR rs1137101 variants were genotyped using the polymerase chain reaction–based restriction fragment length polymorphism method. The genotype distributions of these variants and clinical and laboratory findings were compared.

Results

The LEP rs7799039 GA and AA genotypes and A allele frequencies were higher in participants with MetS than in the control group. For LEP rs7799039, the genotype AA-GA was higher in males, and the GG genotype was higher in females. On analyzing the clinical outcomes associated with these variants, it was observed that individuals possessing LEP rs7799039 GA and AA genotypes displayed elevated levels of triglycerides. In addition, those with the AG-GG genotype of LEPR rs1137101 had lower mean hemoglobin levels.

Conclusion

Our results showed that the LEP rs7799039 and LEPR rs1137101 variants may be associated with both the risk of MetS development and clinical findings. Among the various contributors to MetS, a genetic predisposition is commonly recognized as the primary cause.
Combatant Command Medical Entry Standards
Authors: Hall Andrew , Chenault Janet , Olsen Cara , Medina Sheila , Patel Neha , Hanson Matthew , Matthews Joseph
Published: August 2024

Introduction

The medical entry standards for the United States Central Command (USCENTCOM) restrict individuals with various medical conditions from entering the deployed environment. The impact of this program is unknown.

Materials and Methods

The total number of army personnel deployed to USCENTCOM, the number of individuals with a medical entry waiver adjudicated by United States Army Central (USARCENT), and the evacuation number for each population were compared for calendar year 2023 (CY2023).

Results

A total estimated population of 20,519 U.S. Army personnel were deployed to USCENTCOM. A population of 1,918 received a medical entry waiver due to a disqualifying medical condition. The evacuation rate for the general population was 2.4% compared to the 1.4% evacuation rate of the population with a medical entry waiver (P = .0027).

Conclusion

The medical entry standards, as written and adjudicated in 2023, resulted in a relatively reduced evacuation rate for individuals with otherwise prohibited medical conditions compared to the general deployed population.
Population genomics of the endangered freshwater mussel, Arcidens wheeleri (Unionoidea: Unionidae: Anodontini), in the Little River, Arkansas, USA
Authors: Adcock Mia C , Moles Kendall R , Garrison Nicole L , Donohoo Samantha A , Whelan Nathan V
Published: August 2024

North America is a hotspot of freshwater mussel diversity. However, over the last century, many anthropogenic stressors have led to substantial declines in freshwater mussels of the families Unionidae and Margaritiferidae in North America. Conserving the remaining mussel fauna is a priority, as they play an integral role in freshwater ecosystems. The Little River in Arkansas is home to one of the last remaining populations of the federally endangered freshwater mussel, Arcidens wheeleri (Unionidae: Anodontini). Population dynamics information is lacking for A. wheeleri, and no population genetics study has been conducted on this species. A greater understanding of the genetic diversity within a population can serve as a benchmark for developing an effective management plan. We sampled A. wheeleri from three locations in the Little River. Genomic data were generated with a single-enzyme restriction-site-associated DNA sequencing approach to assess genetic diversity and structure of A. wheeleri in the Little River. Genetic structure analyses indicated one genetic population among the three locations, with limited, fine-scale subpopulation structure. Observed heterozygosity values were considerably lower than expected heterozygosity values, with Ho = 0.14 and He = 0.22, likely indicating a genetic bottleneck. Demographic analysis of the Little River population of A. wheeleri also suggests a historical bottleneck. Furthermore, a high inbreeding coefficient (FIS = 0.33) indicates A. wheeleri in the Little River is losing genetic diversity. Data generated indicate considerable risk of extirpation for A. wheeleri from the Little River and should serve as a baseline for future monitoring. Given its high risk of extinction, we recommend increased study of A. wheeleri across its range and on-the-ground conservation actions that include habitat protection and restoration, which are the only options until a successful host fish and protocols are identified for propagation.
Flexible contracts and ethnic economic inequalities across gender during the UK’s COVID-19 recession
Authors: Ochmann Nico , Clark Ken , Nazroo James , Aparicio-Casto Andrea , Šťastná Michaela
Published: August 2024

Was it their disproportionate presence in flexible employment or in shut-down occupations that made some ethnic minority groups vulnerable to adverse labour market outcomes during the coronavirus disease 2019 (COVID-19) recession? Using the COVID-19 recession in the UK as a case study, we employ weighted linear probability models with 2021 data from the Evidence for Equality National Survey to look at changes in economic indicators across ethnic groups and gender. We report heterogeneity in flexible employment rates within the non-White group and between the non-White and the White British group. By using a conditional decomposition method, we conclude that those ethnic minority groups who were disproportionately on flexible contracts experienced worse economic effects than the White British group.
Assessment of psycho-oncology in the Middle East and North Africa region: a systematic review and meta-analysis
Authors: Al-Hussaini Maysa , Abdel-Razeq Hikmat , Shamieh Omar , Al-Ani Abdallah , Hammouri Muhammad , Mansour Asem
Published: August 2024

Background

The Middle East and North Africa (MENA) region is expected to witness a significant increase in the burden of cancer. Contrary to Western literature, the burden of psycho-oncology is yet to be established within the MENA region. This study reviews all available evidence characterizing the psychological burden among patients with cancer across the MENA region.

Methods

We systematically explored the PubMed/MEDLINE, Cochrane/CENTRAL, and Web of Science (WoS) databases for reports on the psychiatric burden among patients with cancer residing within the MENA region from January 2000 until January 2023. Raw proportion were extracted and analyzed using a random-effects model.

Findings

Eighty-three studies comprised of 16 810 participants, representing 14 countries, met our inclusion criteria. Across the MENA region, the prevalence of depression, anxiety, and distress were 44% (95% CI, 39%-50%), 47% (95% CI, 40%-54%), and 43% (95% CI, 30%-56%), respectively. Prevalence of depression was significantly different across countries, with Palestine (73%; 95% CI, 42%-91%) reporting the highest rate while Morocco (23%; 95% CI, 7%-56%) reported the lowest. Similarly, anxiety significantly differed across MENA nations ranging from 64% (95% CI, 3%-99%) in Morocco to 28% (95% CI, 18%-42%) in Tunisia. Rates of depression and anxiety were significantly different across measurement tools but not between Arabic-speaking versus Persian/Farsi-speaking countries. Meta-regression models showed that neither publication year nor age affected the prevalence of both anxiety and depression (P = .374 and .091 for depression and P = .627, and .546 for anxiety, respectively).

Interpretation

We report an abnormally high rate of psychiatric burden among patients with cancer in the MENA region. Thus, establishing appropriate psycho-oncologic interventions within the MENA region is of utmost importance.
Progenitor and explosion properties of SN 2023ixf estimated based on a light-curve model grid of Type II supernovae
Authors: Moriya Takashi J , Singh Avinash
Published: August 2024

We estimate the progenitor and explosion properties of the nearby Type II SN 2023ixf using a synthetic model grid of Type II supernova light curves. By comparing the light curves of SN 2023ixf with the pre-existing grid of Type II supernovae containing about 228000 models with different combinations of the progenitor and explosion properties, we obtain the $\chi ^2$ value for every model and evaluate the properties of the models providing small values of $\chi ^2$. We found that the light-curve models with a progenitor zero-age main-sequence mass of $10\, {M}_\odot$, explosion energy of $(2\\!-\\!3) \times 10^{51}\:\mbox{erg}$, $^{56}\mbox{Ni}$ mass of 0.04–$0.06\, {M}_\odot$, mass-loss rate of $10^{-3}$–$10^{-2}\, {M}_\odot \:\mbox{yr}^{-1}$ with wind velocity of $10\:\mbox{km}\:\mbox{s}^{-1}$, and dense, confined circumstellar matter radius of $(6\\!-\\!10) \times 10^{14}\:\mbox{cm}$ match well to the observed light curves of SN 2023ixf. The photospheric velocity evolution of these models is also consistent with the observed velocity evolution. We note that the progenitor mass estimate could be affected by the adopted progenitor models. Although our parameter estimation is based on a pre-existing model grid and we do not perform any additional computations, the estimated parameters are consistent with those obtained by the detailed modeling of SN 2023ixf previously reported. This result shows that comparing the pre-existing model grid is a reasonable way to obtain a rough estimate for the properties of Type II supernovae. This simple way to estimate the properties of Type II supernovae will be essential in the Vera C. Rubin Observatory’s Legacy Survey of Space and Time (LSST) era when thousands of Type II supernovae are expected to be discovered yearly.
Feminism, reproductive labour, and the gendered welfare state in Britain’s National Insurance Act of 1911
Authors: Schwartz Laura
Published: August 2024

In 1911, numerous women’s organizations, of varying political interests, mounted a campaign against the National Insurance Bill. Such opposition emerged despite feminist support for increased welfare provision in general and especially for the maternity benefit that the Bill proposed to introduce. Feminists criticized National Insurance for discriminating against women, especially its failure to recognize the economic contribution of women’s unwaged reproductive labour. They lobbied and campaigned for a series of amendments, some of which were successful. Feminist opposition to National Insurance sheds new light on an ongoing historiographical debate over the degree to which women were able to influence early welfare states prior to enfranchisement. Their activities cannot be easily contained within a framework of ‘maternalist feminism’, and call into question distinctions between ‘maternalist’/‘social’ feminism and ‘equality’ feminism, and middle-class and working-class women’s agendas. Instead, feminist campaigns around National Insurance reveal an early analysis of ‘social reproduction’ (the origins of which are usually traced back only to ‘second wave’ feminism) whereby British feminists participated in international conversations contesting the gendered definitions of work that went on to inform insurance-based welfare states across Europe.
High titer expression of antibodies using linear expression cassettes for early-stage functional screening
Authors: Wu Shuang , Tsukuda Joni , Chiang Nancy , Hao To , Chen Yongmei , Hötzel Isidro , Balasubramanian Sowmya , Nakamura Gerald , Kelly Ryan L
Published: August 2024

Antibody discovery processes are continually advancing, with an ever-increasing number of potential binding sequences being identified out of in vivo, in vitro, and in silico sources. In this work we describe a rapid system for high yield recombinant antibody (IgG and Fab) expression using Gibson assembled linear DNA fragments (GLFs). The purified recombinant antibody yields from 1 ml expression for this process are approximately five to ten-fold higher than previous methods, largely due to novel usage of protecting flanking sequences on the 5′ and 3′ ends of the GLF. This method is adaptable for small scale (1 ml) expression and purification for rapid evaluation of binding and activity, in addition to larger scales (30 ml) for more sensitive assays requiring milligram quantities of antibody purified over two columns (Protein A and size exclusion chromatography). When compared to plasmid-based expression, these methods provide nearly equivalent yield of high-quality material across multiple applications, allowing for reduced costs and turnaround times to enhance the antibody discovery process.
Advancements in MR hardware systems and magnetic field control: B0 shimming, RF coils, and gradient techniques for enhancing magnetic resonance imaging and spectroscopy
Authors: Shang Yun , Simegn Gizeaddis Lamesgin , Gillen Kelly , Yang Hsin-Jung , Han Hui
Published: August 2024

High magnetic field homogeneity is critical for magnetic resonance imaging (MRI), functional MRI, and magnetic resonance spectroscopy (MRS) applications. B0 inhomogeneity during MR scans is a long-standing problem resulting from magnet imperfections and site conditions, with the main issue being the inhomogeneity across the human body caused by differences in magnetic susceptibilities between tissues, resulting in signal loss, image distortion, and poor spectral resolution. Through a combination of passive and active shim techniques, as well as technological advances employing multi-coil techniques, optimal coil design, motion tracking, and real-time modifications, improved field homogeneity and image quality have been achieved in MRI/MRS. The integration of RF and shim coils brings a high shim efficiency due to the proximity of participants. This technique will potentially be applied to high-density RF coils with a high-density shim array for improved B0 homogeneity. Simultaneous shimming and image encoding can be achieved using multi-coil array, which also enables the development of novel encoding methods using advanced magnetic field control. Field monitoring enables the capture and real-time compensation for dynamic field perturbance beyond the static background inhomogeneity. These advancements have the potential to better use the scanner performance to enhance diagnostic capabilities and broaden applications of MRI/MRS in a variety of clinical and research settings. The purpose of this paper is to provide an overview of the latest advances in B0 magnetic field shimming and magnetic field control techniques as well as MR hardware, and to emphasize their significance and potential impact on improving the data quality of MRI/MRS.
The Structure of Large SUM-Free Sets in 𝔽n
p
Authors: Versteegen Leo
Published: August 2024

A set $A\subset \mathbb{F}_p^n$ is sum-free if A + A does not intersect A. If $p\equiv 2 \;\mathrm{mod}\; 3$, the maximal size of a sum-free set in $\mathbb{F}_p^n$ is known to be $(p^n+p^{n-1})/3$. We show that if a sum-free set $A\subset \mathbb{F}_p^n$ has size at least $p^n/3-p^{n-1}/6+p^{n-2}$, then there exists subspace $V\lt\mathbb{F}_p^n$ of codimension 1 such that A is contained in $(p+1)/3$ cosets of V. For p = 5 specifically, we show the stronger result that every sum-free set of size larger than $1.2\cdot 5^{n-1}$ has this property, thus improving on a recent theorem of Lev.
Muscle involvement in systemic sclerosis: high mortality not associated with nature of histological lesions
Authors: Le Gouellec Noémie , Zaidan Louai , Chaigne Benjamin , Periou Baptiste , Cailliau Emeline , Dhote Robin , Rivière Sébastien , Uzunhan Yurdagul , Agard Christian , Godeau Bertrand , Wolkenstein Pierre , Hachulla Eric , Mouthon Luc , Authier Jerome
Published: August 2024

Objectives

The aim of this study was to determine the association between various histological patterns and prognosis in patients with SSc and histologically proven muscle involvement.

Methods

A multicentre retrospective study was conducted of a cohort of scleroderma patients who had undergone muscle biopsy. The biopsies were reviewed in a coordinated manner to classify patients based on the histological findings. Three different patterns were observed: fibrosing myopathy (FMy), inflammatory myopathy (IMy), and immune-mediated necrotizing myopathy (IMNMy). Rates of survival, muscle relapse, and cardiac and pulmonary events were compared between these three groups.

Results

Among the 71 scleroderma patients with muscle biopsy specimens available for review, 33 (46.5%) were classified in the FMy group, 18 (25.5%) in the IMy group and 20 (28%) in the NMy group. The median follow-up time was 6.4 years (interquartile range, 2.2–10.9 years), and 21 patients died during follow-up, primarily from heart disease and infections. The 10-year survival rate after the first non-RP symptom was 80%, and the cumulative incidence of muscle relapse was 25%. Neither factor differed significantly between the three groups. The risk of pulmonary events was lowest in the IMy group, significantly lower than in the FMy group (hazard ratio, 0.17; 95% CI, 0.04–0.67) and non-significantly lower than in the IMNMy group (hazard ratio, 0.28; 95% CI, 0.06–1.24). The risk of cardiac events did not differ significantly between the three groups.

Conclusion

The mortality rate in scleroderma patients with muscle involvement was not associated with their histological patterns.