bluuebunny/crossref_metadata_2025 huggingface dataset:
Police evaluation of evidence: statistical format and evidence type
Authors: Cabell Jean J , Livingston Tyler N , Yang Yueran
Published: August 2024

Police must properly evaluate evidence to make consequential decisions. Erroneous evaluations of evidence could begin a process that leads to wrongful convictions through faulty guilt judgments. This study assessed the extent to which police accuracy in judging suspect guilt varied by the statistical format of evidence strength and the type of evidence. We recruited police participants (n = 209) from CloudResearch and randomly assigned them to a 3 (evidence format: LR vs. RMP vs. neutral) x 3 (evidence type: DNA vs. fingerprint vs. eyewitness) between-subjects factorial design. Police participants read a case scenario in which they investigated a murder case and evaluated suspect guilt based on a piece of evidence. Prior odds of guilt were controlled for as 1 in all conditions. In general, police under-weighed evidence in the RMP format and were more accurate at judging suspect guilt when the evidence was in the LR format and when the evidence was inconclusive. The effect of evidence format was particularly strong for DNA evidence. Additionally, police participants’ responses did not differ between different guilt measures. Overall, police showed inconsistencies in their guilt judgments when evaluating evidence with different statistical formats and evidence types.
Molecular analysis of cutaneous yeast isolates in the mycobiota of children with atopic dermatitis
Authors: Vial Iwyna França Souza Gomes , Voidaleski Morgana Ferreira , Lameira Rosângela Ferreira , Costa Flavia de Fatima , Zanatta Danielle Arake , Vicente Vania Aparecida , de Carvalho Vania Oliveira
Published: August 2024

The skin of patients with atopic dermatitis (AD) has a greater diversity of mycobiota. An observational, prospective, cross-sectional, analytical, and comparative study was conducted involving 80 patients with AD Group (ADG) and 50 individuals without AD (wADG) in a tertiary hospital in Brazil. Skin scale samples were collected from the frontal, cervical, fossae cubital, and popliteal regions and identified using molecular biology techniques. The results showed that 47.5% of ADG had identified yeasts compared to 0% of wADG (P < .001). The yeasts Rhodotorula mucilaginosa and Candida parapsilosis were the most abundant. The probability of colonization increased with age, showing values of 40% at 60 months and 80% at 220 months (P = .09). The cervical region (12.5%) was colonized to the greatest extent. Our findings revealed that positive mycology was not more probable when the scoring of atopic dermatitis or eczema area and severity index value increased (P = .23 and .53, respectively). The results showed that the sex, age, and different population types directly affected the composition of the mycobiota in the population analyzed. A higher frequency of colonization and greater diversity of yeast species were detected in the cutaneous mycobiota of children with AD.
The effect of local photoionization on the galaxy properties and the circumgalactic medium in simulations of Milky Way-sized galaxies
Authors: Zhu Bocheng , Springel Volker
Published: August 2024

In this study, we investigate the impact of local stellar radiation in cosmological zoom simulations of the formation of Milky Way-sized galaxies. We include the radiation field as an additional feedback component that is computed alongside gravity with a tree code in an optically thin approximation. We resimulate the initial conditions of five Milk Way-like systems taken from the Auriga project with and without stellar radiation, and study the effects of local stellar radiation on several properties of the galaxies and the circumgalactic medium (CGM). Similar to previous findings, we observe with our current model that local stellar radiation can modify gas cooling in the CGM and thus suppress star formation and the surface densities of young stars and H i gas, while having little impact on the total gas content. In particular, it also suppresses the peak of the rotation curve and reduces the mass of the stellar bulge. In the CGM region, the young stellar radiation exceeds the external ultraviolet background and dominates the radiation field within the virial halo at all redshifts. Nevertheless, we find that the local stellar radiation, as implemented in the current study, has overall little impact on the radial density and temperature profile of the CGM gas. However, for the ion species H i and Mg ii, the column densities within $\sim 0.3\, R_{\rm vir}$ are reduced, while the O vi column density is hardly impacted by the radiation field due to a lack of soft X-ray components in our current model. Additional effects can be expected from the radiation of the central active galactic nucleus during phases of quasar activity and from soft X-ray sources, which have not yet been included in the simulations of the present study.
The kidney–skeletal muscle–heart axis in chronic kidney disease: implications for myokines
Authors: Quiroga Borja , Díez Javier
Published: August 2024

Myokines are signalling moieties released by the skeletal muscle in response to acute and/or chronic exercise, which exert their beneficial or detrimental effects through paracrine and/or autocrine pathways on the skeletal muscle and through endocrine pathways in many other organs (e.g. the heart). Interestingly, alterations in myokines have been described in patients with heart failure (HF) that are associated with adverse structural and functional left ventricular remodelling and poor cardiac outcomes. Recent experimental and clinical studies have shown that the muscle regulation of a number of myokines is altered in chronic kidney disease (CKD) thus representing a new molecular aspect of the pathophysiology of skeletal myopathy present in patients with CKD. Muscle dysregulation of myokines may contribute to a number of disorders in non-dialysis and dialysis patients with CKD, including the high risk of developing HF. This possibility would translate into a range of new diagnostic and therapeutic options. In fact, the measurement of circulating myokines opens their possible usefulness as biomarkers to personalize exercise training and pharmacological therapies for the prevention and treatment of HF in patients with CKD and skeletal myopathy. This review will analyse information on some myokines that target the heart and are altered at the level of skeletal muscle and circulation in patients with CKD.
Association Between Antibodies That Bind Epstein-Barr Virus (EBV) gp350 and gH/gL and Shedding of EBV in Saliva From Nasopharyngeal Carcinoma Multiplex Family Members in Taiwan
Authors: Liu Kai-Lin , Hsu Wan-Lun , Bu Wei , Yu Kelly J , Wang Cheng-Ping , Chien Yin-Chu , Chen Tseng-Cheng , Chen Chien-Jen , Hildesheim Allan , Middeldorp Jaap M , Waterboer Tim , Cohen Jeffrey I , Coghill Anna E , Liu Zhiwei
Published: August 2024

Elevated levels of Epstein-Barr virus (EBV) gp350 and gH/gL antibodies have been associated with a lower risk of developing nasopharyngeal carcinoma (NPC), although the evidence remains inconclusive and unexplained. We conducted a longitudinal study within a high-risk Taiwanese cohort, analyzing total immunoglobulin against EBV-gp350 and -gH/gL in blood and EBV DNA shedding in saliva. Contrary to our hypothesis—that elevated levels of antibodies previously shown to be associated with a lower NPC risk should result in a decrease in EBV shedding in saliva—higher anti-gp350 antibodies at baseline were significantly associated with detectable EBV DNA in saliva at follow-up (odds ratio [OR], 1.99 [95% confidence interval {CI}, 1.03–3.97]; P = .04). Higher anti-EBV-gH/gL antibodies at baseline were not significantly associated with risk of detectable EBV DNA at follow-up (OR, 0.69 [95% CI, .35–1.32]; P = .26). These findings underscore the complexity of virus–host interactions and emphasize the need for further investigations into their role in EBV-associated diseases.
Unconditional Love, Some Implications for the Law
Authors: Allen Anita L
Published: August 2024

Love is a rich topic for recent moral philosophers, theologians, writers and social justice activists. Yet, normative concepts of love embedded in modern law are seldom closely examined by legal theorists. This article is the first to illustrate that the concept of unconditional love plays significant roles across diverse areas of the positive law. Relying on a stipulated ethical understanding of unconditional love as a durable, constant, loyal, faithful, generous and self-sacrificing love, I demonstrate that, for better or worse, law can serve unconditional love’s paramount demands. Significant categories of contemporary legal regulation are explicable to the communities bound by them because the evocative notion that some familial love is and ought to be ‘unconditional’ is socially pervasive. I do not advocate for the problematic concept of unconditional love but demonstrate that the law embeds it in two ways. One way is by affording opportunities for individuals voluntarily to exercise the felt imperatives of unconditional love (eg through prison visitation rights and spousal testimonial privileges). The other is by imposing duties of unconditional love that may run strongly counter to individuals’ choices and preferences (eg by restricting access to safe abortion and requiring parental support of adult children). I suggest that derelict and gender-biased governments may shun their own social welfare responsibilities by imposing on private individuals caregiving duties that bespeak unconditional love. Attention to the powerful unconditional love concepts embedded throughout the law can foster an improved understanding of the norms and politics of marriage and family governance.
Women’s Health Across the Lifespan: A Sex- and Gender-Focused Perspective
Authors: McKinney Jessica L , Clinton Susan C , Keyser Laura E
Published: August 2024

Women’s health in physical therapy has historically focused on sexual and reproductive health. The biological and social constructs of sex and gender, respectively, are determinants of health, including pathophysiology of disease and therapeutic outcomes, and an expansion of the concept of “women’s health” is warranted. This Perspective explores the role of sex and gender as key determinants of women’s and girls’ health and highlights the factors pertinent to physical therapist practice. The Scale for the Assessment for Narrative Review Articles (SANRA), a 6-point assessment to evaluate the quality of narrative reviews, was used a priori and consulted throughout. Across the lifespan, sex- and gender-based health disparities exist. These include sex-based disparities in maternal–fetal outcomes linking female fetal sex to maternal hypertensive disorders of pregnancy, along with a sex-based female advantage in birth outcomes and the emergence of gender differences in motor development. A complex interplay of biological and socially influenced factors contributes to an increased care burden for women throughout adulthood and specific risks for the development of cardiovascular and pelvic floor conditions, decreased function, and increased disability. Sex- and gender-disaggregated data are lacking in outcomes literature. A sex- and gender-informed approach in physical therapy, including analyzing data by sex and gender, may better meet the needs of patients and better prepare physical therapist professionals to contribute to women’s health across the lifespan. Success will take coordinated effort involving many stakeholders within and adjacent to the physical therapist community. The influence of sex and gender are lifelong determinants of health, making them critically important to consider in physical therapist practice, education, research, advocacy, and policy. In women’s health, focusing on sexual and reproductive health is limiting and insufficient.
SMILE Winter Campaign
Authors: Walach M -T , Soobiah Y , Carter J A , Whiter D K , Kavanagh A J , Hartinger M D , Oksavik K , Salzano M L , Archer M O
Published: August 2024

This white paper is highly topical as it relates to the upcoming solar wind magnetosphere ionosphere link explorer (SMILE) mission: SMILE is a joint mission between the European Space Agency and the Chinese Academy of Sciences and it aims to build a more complete understanding of the Sun–Earth connection by measuring the solar wind and its dynamic interaction with the magnetosphere. It is a fully funded mission with a projected launch in 2025. This paper outlines a plan for action for SMILE’s first Northern hemisphere winter campaign using ground-based instruments. We outline open questions and which data and techniques can be employed to answer them. The science themes we discuss are: (i) Earth’s magnetosheath, magnetopause, and magnetic cusp impact on the ionospheric cusp region; (ii) defining the relationship between auroral processes, solar wind, and magnetospheric drivers; (iii) understanding the interhemispheric properties of the Earth’s magnetosphere–ionosphere system. We discuss open questions (different to the mission goals) which may be answered using existing ground-based instrumentation together with SMILE data to leverage the maximum scientific return of the mission during the first winter after launch. This paper acts as a resource for planning, and a call to collaborative action for the scientific community.
Dose of phytase from either Aspergillus niger or Escherichia coli on performance of nursery piglets
Authors: Pereira Francisco Alves , Coelho Flavio Aguiar , Alves Laya Kannan Silva , dos Santos Fernanda Mariane , Pereira Erick Marlon , Silva Neta Clarice Speridiao , Ferreira Felipe Norberto Alves , da Cunha Ana Caroline Rodrigues , Pairis-Garcia Monique Danielle , Garbossa Cesar Augusto Pospissil
Published: August 2024

Supplementing swine diets with phytase increases phosphorus release by approximately 50% from cereal phytates. The increase in phosphorus availability allows for a reduction in dietary phosphorus supplementation from mineral sources and decreases the environmental impact of pork production through a decrease in phosphorus excretion. Superdosing phytase has been reported to boost swine productivity, improve the digestibility of other nutrients, and mitigate the antinutritional effects of phytates. However, there are significant cost differences among phytase products. Bacterial phytases are considered more modern, often with a higher cost of inclusion. A study was conducted with 288 piglets that were 21 d of age and weighed 6.43 ± 0.956 kg. Pigs were divided into four groups. Each group of pigs was fed a different experimental diet varying in phytase source and level: fungal phytase (Aspergillus niger) at 500 FTU/kg of diet, fungal phytase at 2,000 FTU/kg, bacterial phytase (Escherichia coli) at 500 FTU/kg, and bacterial phytase at 2,000 FTU/kg. No differences were found for phytase sources or doses on productivity at 14 and 21 d postweaning. However, piglets supplemented with 2,000 FTUs/kg of phytase in the diet during the first 21 d of nursery exhibited a 5.8% better feed conversion (P = 0.02). An interaction between phytase source and dose was observed for average live weight and daily weight gain over the 42-d nursery period (P < 0.05). Supplementing the diet with 2,000 FTU/kg of fungal phytase improved daily weight gain and live weight throughout the experimental period compared to piglets supplemented with 500 FTU/kg of the same phytase source. Additionally, it resulted in better final weights compared to piglets supplemented with 500 FTU/kg of bacterial phytase. Phytase inclusion at 2,000 FTU/kg improved feed conversion by 2.07% over the 42-d nursery period. The most economically favorable feed conversion ratios were observed when supplementing the diet with fungal phytase at 2,000 FTUs/kg.
Identifying indicators of apple bud dormancy status by exposure to artificial forcing conditions
Authors: Milyaev Anton , Born Ute , Sprich Elke , Hagemann Michael , Flachowsky Henryk , Luedeling Eike
Published: August 2024

Dormancy in temperate fruit trees is a mechanism of temporary growth suspension, which is vital for tree survival during winter. Studies on this phenomenon frequently employ scientific methods that aim to detect the timing of dormancy release. Dormancy release occurs when trees have been exposed to sufficient chill, allowing them to resume growth under conducive conditions. This study investigates dormancy dynamics in two apple (Malus × domestica Borkh.) cultivars, ‘Nicoter’ and ‘Topaz’, by sampling branches in an orchard over 14 weeks (2019 to 2020) and over 31 weeks (2021 to 2022) and subjecting them to a 42-day budbreak forcing period in a growth chamber. Temporal changes in budbreak percentages demonstrated dormancy progression in the studied apple cultivars and allowed the three main dormancy phases to be distinguished: paradormancy (summer dormancy), endodormancy (deep dormancy) and ecodormancy (spring dormancy), along with transition periods between them. Using these data, we explored the suitability of several alternative methods to determine endodormancy release. Tabuenca’s test, which predicts dormancy release based on the differences in dry weights of buds with and without forcing, showed promise for this purpose. However, our data indicated a need for considerable adjustments and validation of this test. Bud weight and water content of buds in the orchard did not align with budbreak percentages under forcing conditions, rendering them unsuitable for determining endodormancy release in ‘Nicoter’ and ‘Topaz’. Shoot growth cessation did not seem to be connected with either dormancy progression or dormancy depth of the studied cultivars, whereas leaf fall coincided with the beginning of the transition from endo- to ecodormancy. This work addresses methodological limitations in dormancy research and suggests considering the mean time to budbreak and budbreak synchrony as additional criteria to assess tree dormancy status.
Incidence, aetiology and short term outcomes of extreme hyperbilirubinaemia, in term infants born in the Western health subdistrict of Cape Town, South Africa between 2019 and 2020
Authors: Coraizin Carin , Vreede Heleen , Van Niekerk Cara , Joolay Yaseen
Published: August 2024

Extreme levels of bilirubin in newborn is a major cause of lifelong neurodevelopmental impairment, which places a financial burden on healthcare resources and caregivers. To determine the incidence, aetiology and short-term outcomes of extreme hyperbilirubinaemia in term infants born in a resource-limited setting. This is a retrospective observational study looking at term neonates with a birth weight ≥2500 g, born in the Western health subdistrict of Cape Town, South Africa, between 1 January 2019 and 31 December 2020, who were exposed to a serum bilirubin level of ≥430 μmol/L in the first week of life and received care in the public health system. Extreme hyperbilirubinaemia occurred in 59 term infants. The incidence was 74 cases per 100 000 (<0.01%) live births equating to 1 case in every 1345 live births. The cause of hyperbilirubinaemia was identified in 51 of the cases (86%), the most common being ABO incompatibility (31/51, 61%), followed by glucose-6-phosphate dehydrogenase deficiency (11/51, 22%). Twelve infants (20 %) underwent an exchange transfusion. Six infants were encephalopathic. Forty-seven infants (80%) were readmitted after initial post-natal discharge, with a mean age of readmission of 113 h old (SD 31 h). The incidence of extreme hyperbilirubinaemia in the Western health subdistrict of Cape Town is higher than in high-income settings. Further work should focus on training of healthcare workers and education of caregivers, for the early detection of significant hyperbilirubinaemia to prevent neurological complications caused by bilirubin toxicity.
Virulence, Structure, and Triadimefon Sensitivity of the Puccinia striiformis f. sp. tritici Population in Shaanxi Province, China
Authors: Zhou Aihong , Xia Minghao , Chen Xianming , Feng Yaoxuan , Liu Xinyun , Jin Yongjin , Huang Lili , Kang Zhensheng , Zhan Gangming
Published: August 2024

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is the most destructive fungal disease affecting wheat in China, especially in Shaanxi Province, an important epidemiological region connecting the western Pst oversummer regions and the central and eastern spring epidemic regions in the country. In the present study, 291 Pst isolates from Shaanxi Province were studied for their virulence using two sets of wheat differentials, population structure using single-nucleotide polymorphism (SNP) markers, and sensitivity to triadimefon. When the isolates were tested on the Chinese differentials of 19 wheat cultivars, 72 races were identified, which belonged to three groups, including the Guinong 22 group (48.45%), Hybrid 46 group (31.62%), and Suwon 11 group (19.93%). The three most predominant races were CYR34 (15.46%), G22-14 (11.68%), and CYR32 (10.65%). When the isolates were tested on the 18 Yr single-gene differentials, 95 races were identified, but none of the isolates were virulent to either Yr5 or Yr15. Cluster analyses of the virulence data based on the two sets of differentials and the SNP marker data consistently separated the Shaanxi Pst population into two clusters in the central part and southern part of the province. Triadimefon sensitivity testing across different concentrations showed a broad range of half-maximal effective concentration (EC50) values, from 0.03 to 5.99 μg ml−1, with a mean EC50 value of 0.46 μg ml−1. The majority of isolates (90.72%) were sensitive to the fungicide. The correlation analyses of the virulence, SNP marker, and the triadimefon sensitivity data showed no significant correlations, except a logarithmic relationship between the EC50 value and the number of avirulence factors. This study is the first to determine the relationship of virulence and SNP markers with triadimefon sensitivity in a regional Pst population. The findings provide valuable insights for breeding resistant wheat cultivars and integrated management of stripe rust.
VEGF‐B prevents chronic hyperglycemia‐induced retinal vascular leakage by regulating the CDC42‐ZO1/VE‐cadherin pathway
Authors: Xu Yuxue , Peng Yue , Wu Xiaojun , Ni Feixue , Sun Daxi , Zhang Pengfei , Yang Yang , Yan Miao , Mi Jia , Tian Geng
Published: August 2024

Non‐proliferative diabetic retinopathy (NPDR) is the early stage of diabetic retinopathy (DR) and is a chronic oxidative stress‐related ocular disease. Few treatments are approved for early DR. This study aimed to investigate the pathogenic mechanisms underlying the retinal micro‐vasculopathy induced by diabetes and to explore an early potential for treating early DR in a mouse model. The mouse model of type 1 diabetes was established by intraperitoneal injection of streptozotocin (STZ, 180 mg/kg), which was used as the early DR model. The body weight and blood glucose mice were measured regularly; The retinal vascular leakage in the early DR mice was determined by whole‐mount staining; Label‐free quantitative proteomic analysis and bioinformatics were used to explore the target proteins and signaling pathways associated with the retinal tissues of early DR mice; To detect the effects of target protein on endothelial cell proliferation, migration, and tube formation, knockdown and overexpression of VEGF‐B were performed in human retinal vascular endothelial cells (HRECs); Western blotting was used to detect the expression of target proteins in vitro and in vivo; Meanwhile, the therapeutic effect of VEGF‐B on vascular leakage has also been evaluated in vitro and in vivo. The protein expressions of vascular endothelial growth factor (VEGF)‐B and the Rho GTPases family member CDC42 were reduced in the retinal tissues of early DR. VEGF‐B upregulated the expression of CDC42/ZO1/VE‐cadherin and prevented hyperglycemia‐induced vascular leakage in HRECs. Standard intravitreal VEGF‐B injections improved the retinal vascular leakage and neurovascular response in early DR mice. Our findings demonstrated, for the first time, that in diabetes, the retinal vessels are damaged due to decreased VEGF‐B expression through downregulation of CDC42/ZO1/VE‐cadherin expression. Therefore, VEGF‐B could be used as a novel therapy for early DR.
Performance of the Washington Group Questions in Measuring Blindness and Deafness
Authors: Landes Scott D. , Swenor Bonnielin K. , Hall Jean P.
Published: August 2024

The Washington Group Short Set (WGSS) questions are intended to measure the severity of disability and disability status in US federal surveys. We used data from the 2010-2018 National Health Interview Survey to examine the performance of the WGSS visual disability and hearing disability questions in capturing blindness and deafness. We found that the WGSS questions failed to capture 35.7% of blind adults and 43.7% of deaf respondents as having a severe disability, or, per their recommended cut point, as being disabled at all. Coupled with prior evidence demonstrating the poor performance of the WGSS questions in estimating the size of the overall disability population, we contend that results from this study necessitate a pause in use of the WGSS questions to measure disability in US federal surveys.
cfGWAS reveal genetic basis of cell-free DNA features
Authors: Zhu Huanhuan , Zhang Yan , Zeng Shuang , Li Linxuan , Ou Rijing , Zhang Xinyi , Lin Yu , Lin Ying , Xu Chuang , Wang Lin , Zeng Guodan , Zeng Jingyu , Li Lingguo , Jia Yongjian , Wang Yu , Luo Fei , Yang Meng , Hu Yuxuan , Li Xiameizi , Xiao Han , Xu Xun , Wang Jian , Zhou Aifen , Zhang Haiqiang , Jin Xin
Published: August 2024

cfDNA consists of degraded DNA fragments released into body fluids. Its genetic and pathological information makes it useful for prenatal testing and early tumor detection. However, the mechanisms behind cfDNA biology are largely unknown. In this study, for the first time, we conducted a GWAS study to explore the genetic basis of cfDNA features, termed cfGWAS, in 28,016 pregnant women. We identified 84 significant loci, including well-known cfDNA-related genes DFFB and DNASE1L3, and numerous novel genes potentially involved in cfDNA biology, including PANX1 and DNASE1L1. The findings were further verified through independent GWAS and experimental validation in knockout mice and cell lines. Subsequent analyses revealed strong causal relationships of hematological indicators on cfDNA features. In summary, we presented the first cfGWAS, revealing the genetic basis of cfDNA biology from genome-wide scale. Novel knowledge uncovered by this study keep the promise to revolutionize liquid biopsy technology and potential new drug targeted for certain disease. Given exist of the millions cfDNA whole-genome-sequencing data generated from clinical testing, the potential of this paradigm is enormous.
Technical Development and In Silico Implementation of SyntheticMR in Head and Neck Adaptive Radiation Therapy: A Prospective R-IDEAL Stage 0/1 Technology Development Report
Authors: McCullum Lucas , Mulder Samuel , West Natalie , Aghoghovbia Robert , Ali Alaa Mohamed Shawky , Scott Hayden , Salzillo Travis C. , Ding Yao , Dresner Alex , Subashi Ergys , Ma Dan , Stafford R. Jason , Hwang Ken-Pin , Fuller Clifton D.
Published: August 2024

Objective

The purpose of this study was to investigate the technical feasibility of integrating the quantitative maps available from SyntheticMR into the head and neck adaptive radiation oncology workflow. While SyntheticMR has been investigated for diagnostic applications, no studies have investigated its feasibility and potential for MR-Simulation or MR-Linac workflow. Demonstrating the feasibility of using this technique will facilitate rapid quantitative biomarker extraction which can be leveraged to guide adaptive radiation therapy decision making.

Approach

Two phantoms, two healthy volunteers, and one patient were scanned using SyntheticMR on the MR-Simulation and MR-Linac devices with scan times between four to six minutes. Images in phantoms and volunteers were conducted in a test/retest protocol. The correlation between measured and reference quantitative T1, T2, and PD values were determined across clinical ranges in the phantom. Distortion was also studied. Contours of head and neck organs-at-risk (OAR) were drawn and applied to extract T1, T2, and PD. These values were plotted against each other, clusters were computed, and their separability significance was determined to evaluate SyntheticMR for differentiating tumor and normal tissue.

Main Results

The Lin’s Concordance Correlation Coefficient between the measured and phantom reference values was above 0.98 for both the MR-Sim and MR-Linac. No significant levels of distortion were measured. The mean bias between the measured and phantom reference values across repeated scans was below 4% for T1, 7% for T2, and 4% for PD for both the MR-Sim and MR-Linac. For T1 vs. T2 and T1 vs. PD, the GTV contour exhibited perfect purity against neighboring OARs while being 0.7 for T2 vs. PD. All cluster significance levels between the GTV and the nearest OAR, the tongue, using the SigClust method was p < 0.001.

Significance

The technical feasibility of SyntheticMR was confirmed. Application of this technique to the head and neck adaptive radiation therapy workflow can enrich the current quantitative biomarker landscape.
SNP Genes Effect on Thyroid Disorders in a Chinese Demographic
Authors: Fan Iris , Zhou Fenglan
Published: August 2024

Thyroid disorders, particularly hypothyroidism, are prevalent in the Chinese population and have been linked to specific genetic variations. This study investigates the associations between single nucleotide polymorphisms (SNPs) and thyroid disorders in a cohort of Chinese individuals. It aims to explore a novel aspect of thyroid disorders, precisely the effect of different SNPs on the prevalence of developing these disorders, autoimmune diseases, or cancer. It focuses on four SNPs: rs965513, rs179247, rs3087243, and rs231779. The analysis revealed significant associations between these SNPs and thyroid disorders, with the ‘A’ allele of rs179247 showing a higher risk.
Global and regional burden of ischemic stroke disease from 1990 to 2021: an age-period cohort analysis
Authors: Zhu Weimin , He Xiaxia , Huang Daochao , Jiang Yiqing , Hong Weijun , Ke Shaofa , Wang En , Wang Feng , Wang Xianwei , Shan Renfei , Liu Suzhi , Xu Yinghe , Jiang Yongpo
Published: August 2024

Background

Ischemic stroke is a major global public health concern. This study evaluates the burden of ischemic stroke in 2021, analyzes trends since 1990, and predicts future burdens.

Methods

Data were sourced from the Global Burden of Disease Study 2021, focusing on incidence, mortality, and disability-adjusted life years (DALYs) on a global, regional, and all socio-demographic index area (SDI) basis. Joinpoint regression and age-period-cohort modeling were employed for trend analysis.

Results

In 2021, there were 7,804,449 (95% UI, 6,719,760 - 8,943,692) global ischemic stroke patients, resulting in 3,591,499 (95% UI, 3,213,281 - 3,888,327) deaths and 70,357,912 (95% UI, 64,329,576 - 76,007,063) DALYs. East Asia had the highest number of cases, while Eastern Europe had the highest age-standardized incidence rate. High-income countries reported the lowest rates of incidence, mortality, and DALYs, which are significantly declining overall. From 1990 to 2021, the age-standardized incidence rate decreased by -0.578% annually, mortality by -0.927%, and DALYs by -14.372%. The rates are influenced by age, time, and cohorts, generally increasing with age but declining over time, especially in high SDI regions. Key risk factors include hypertension, environmental pollution, and high low density lipoprotein cholesterol, with hypertension having the most significant and stable impact. Projections for 2035 suggest worsening ischemic stroke outcomes for those over 45, while improvements are expected for individuals under 35. The 50-59 age group’s age-standardized incidence rate may rise, but mortality and DALYs rates are expected to decline across all ages.

Conclusion

Our study shows a decline in ischemic stroke mortality and incidence, yet its global burden is rising due to aging populations and persistent health issues. This highlights the importance of targeting prevention and treatment, particularly for those over 45. Future efforts must tackle high rates in affected areas and address key risks like hypertension and high cholesterol.
Prolonged viral shedding as a marker of severity in respiratory syncytial virus bronchiolitis
Authors: Watanabe Raí André Silva , Nishiyama Filipe , Lyra Larissa , Camargo Bruno Sanchez , de Souza Luna Luciano Kleber , Conte Danielle Dias , Perosa Ana Helena , Bellei Nancy Cristina Junqueira
Published: August 2024

Background and Objectives

Respiratory syncytial virus (RSV) is responsible for most cases of acute viral bronchiolitis (AVB) in childhood. The association of factors such as RSV subtype, viral load, and viral coinfection with severe disease is controversial. The objective is to describe the viral load dynamics of RSV in children under 2 years with AVB, including the first viral load, peak viral load, viral decay, and any possible association with severe disease.

Methods

73 inpatients with AVB and confirmed RSV infection were included. Viral load was obtained through nasal swab samples daily during hospitalization and weekly after discharge until absence of detection.

Results

44 of the patients were male, the mean age was 5.76 months, and comorbidities were found in 15 (20.5%) of the patients. 54 (74%) of the patients had the peak viral load between the 4th and the 7th day of symptom onset. The mean duration of viral detection was 12.5 days. There was no association between the first and peak viral load with markers of severe disease. However, association was found between viral persistence exceeding 10 days and the following factors: longer hospitalization period (p=0.009), length of ventilation support (p=0.044), length of invasive mechanical ventilation (p=0.035), prolonged requirement of nutritional support (p=0.038), and a longer course of antibiotic treatment (p=0.024). Age was inversely correlated with most of the severity outcomes.

Conclusion

Despite the lack of association between RSV viral load values and disease severity, prolonged viral shedding was associated with several adverse outcomes, which can contribute to a better understanding of RSV disease, particularly as several interventions are anticipated to become available in the coming years.
Continuous vital sign monitoring of individuals with acute Lassa fever using wearable biosensor devices
Authors: Page Brady , Klitting Raphaëlle , Pauthner Matthias G. , Steinhubl Steven , Wegerich Stephan , Kaiser Margaret , Alhasan Foday , Konuwa Edwin , Koroma Veronica , Sumah Ibrahim , Brima Jenneh , Kallon Tiangay , Jusu Brima , Mator-Mabay Sia , Massaquoi Isata , Kamara Mohamed , Kamara Fatima , Jaward Emilia , Massally Angella , Kanneh Zainab , McGraw Michelle , Schieffelin John , Grant Donald , Andersen Kristian G.
Published: August 2024

Background

Lassa fever is a fulminant viral illness associated with high in-hospital mortality. This disease constitutes a serious public health concern in West Africa, in particular Nigeria and the Mano River Union region (Guinea, Liberia, and Sierra Leone). In Sierra Leone, continuous monitoring of critically ill patients is hindered by a lack of equipment and personnel.

Methods

We used wearable biosensor devices to remotely monitor hospitalized individuals with acute Lassa fever in order to describe vital sign trends that may be associated with clinical outcome and to evaluate the feasibility of this approach in a resource-limited setting.

Results

The case fatality rate among participants (n=8) was 62.5%, with a median time from hospital admission to death of 2 days. Our results show that individuals who died (n=5) had higher mean heart rate (126 beats per minute) and respiratory rate (29 breaths per minute), as well as lower mean heart rate variability (10 ms), compared to those that survived (63 beats per minute, 22 breaths per minute, and 59 ms, respectively). Non-survivors also spent a greater proportion of their monitoring period in the age-specific tachycardia range (45.8%) compared to survivors (1.7%).

Conclusions

Although real-time monitoring of vital signs using wearable biosensors may have the potential to identify decompensations earlier than traditional bedside vital sign collection in a resource-limited setting, technical improvements are still needed to enable widespread use of this tool, for both clinical and research purposes.
PREDICTORS OF UNMET NEEDS OF FAMILY PLANNING AMONG WOMEN IN THEIR REPRODUCTIVE AGES LIVING WITH HIV IN SUB-SAHARAN AFRICA: ANALYSIS OF DEMOGRAPHIC HEALTH SURVEY
Authors: Koray Munawar Harun , Mshenga Mansour Maulid , Mwanja Epafra Luka , Sulieman Sara , Punguyire Damien , Adomah-Afari Augustine
Published: August 2024

Background

Unmet needs for family planning (FP) among women of reproductive age living with HIV (WRLWH) increase the risk of mother-to-child transmission (MTCT) of HIV, hindering efforts to control the epidemic. These unmet needs lead to unintended pregnancies among high-risk mothers, resulting in maternal health complications, and risk of MTCT of HIV. This study examines factors predicting unmet FP needs among WRLWH in Sub-Saharan Africa (SSA).

Method

This cross-sectional study used secondary data from the Demographic Health Survey (DHS) program, encompassing 14 SSA countries and including 9395 WRLWH. Data analysis, conducted with STATA version 18, involved three steps: computing unmet FP needs using descriptive statistics, assessing associations through Pearson’s chi-square test, and performing multi-level regression analysis to identify predictors of unmet FP needs. Regression models were fitted, considering individual factors, FP exposure, and partner/community factors, with statistical significance set at p-value ≤ 0.05 at a 95% confidence interval. Both random effects and fixed effects were reported.

Results

The findings revealed that 15.57% of the WRLWH had unmet FP needs. Older aged women with HIV had lower odds of unmet FP needs, particularly the 45-49 age group (aOR = 0.159, CI = 0.0913-0.277). Higher parity increased the odds, especially for those with four or more children (aOR = 8.081, CI = 5.113-12.77). Exposure to FP through media reduced the odds (aOR = 0.564, CI = 0.468-0.678). Female household heads had higher odds (aOR = 1.306, CI = 1.086-1.571) of unmet need of FP, while rural residents had lower odds (aOR = 0.696, CI = 0.560-0.866) compared to urban residents.

Conclusion

The study highlights the necessity for tailored FP programs and targeted media-based education to reduce unmet needs among WLWH, enhance health outcomes, prevent MTCT of HIV, and achieve related SDGs among women in their reproductive age living in SSA.
Role of AMPK in Atrial Metabolic Homeostasis and Substrate Preference
Authors: Toksoy Zeren , Ma Yina , Goedeke Leigh , Li Wenxue , Hu Xiaoyue , Wu Xiaohong , Cacheux Marine , Liu Yansheng , Akar Fadi G. , Shulman Gerald I. , Young Lawrence H.
Published: August 2024

Atrial fibrillation is the most common clinical arrhythmia and may be due in part to metabolic stress. Atrial specific deletion of the master metabolic sensor, AMP-activated protein kinase (AMPK), induces atrial remodeling culminating in atrial fibrillation in mice, implicating AMPK signaling in the maintenance of atrial electrical and structural homeostasis. However, atrial substrate preference for mitochondrial oxidation and the role of AMPK in regulating atrial metabolism are unknown. Here, using LC-MS/MS methodology combined with infusions of [13C6]glucose and [13C4]β-hydroxybutyrate in conscious mice, we demonstrate that conditional deletion of atrial AMPK catalytic subunits shifts mitochondrial atrial metabolism away from fatty acid oxidation and towards pyruvate oxidation. LC-MS/MS-based quantification of acyl-CoAs demonstrated decreased atrial tissue content of long-chain fatty acyl-CoAs. Proteomic analysis revealed a broad downregulation of proteins responsible for fatty acid uptake (LPL, CD36, FABP3), acylation and oxidation. Atrial AMPK deletion reduced expression of atrial PGC1-α and downstream PGC1-α/PPARα/RXR regulated gene transcripts. In contrast, atrial [14C]2-deoxyglucose uptake and GLUT1 expression increased with fasting in mice with AMPK deletion, while the expression of glycolytic enzymes exhibited heterogenous changes. Thus, these results highlight the crucial homeostatic role of AMPK in the atrium, with loss of atrial AMPK leading to downregulation of the PGC1-α/PPARα pathway and broad metabolic reprogramming with a loss of fatty acid oxidation, which may contribute to atrial remodeling and arrhythmia.
Do fungi look like macroparasites? Quantifying the patterns and mechanisms of aggregation for host-fungal parasite relationships
Authors: Schrock Sarah A.R. , Walsman Jason C. , DeMarchi Joseph , LeSage Emily H. , Ohmer Michel E.B. , Rollins-Smith Louise A. , Briggs Cheryl J. , Richards-Zawacki Corinne L. , Woodhams Douglas C. , Knapp Roland A. , Smith Thomas C. , Haddad Célio F.B. , Guilherme Becker C. , Johnson Pieter T.J. , Wilber Mark Q.
Published: August 2024

Most hosts contain few parasites, whereas few hosts contain many. This pattern, known as aggregation, is well-documented in macroparasites where parasite intensity distribution among hosts affects host-parasite dynamics. Infection intensity also drives fungal disease dynamics, but we lack a basic understanding of host-fungal aggregation patterns, how they compare to macroparasites, and if they reflect biological processes. To address these gaps, we characterized aggregation of the fungal pathogenBatrachochytrium dendrobatidis(Bd) in amphibian hosts. Utilizing the slope of Taylor’s Power Law, we found Bd intensity distributions were more aggregated than macroparasites, conforming closely to lognormal distributions. We observed that Bd aggregation patterns are strongly correlated with known biological processes operating in amphibian populations, such as epizoological phase—invasion, post-invasion, and enzootic—and intensity-dependent disease mortality. Using intensity-dependent mathematical models, we found evidence of evolution of host resistance based on aggregation shifts in systems persisting with Bd following disease-induced declines. Our results show that Bd aggregation is highly conserved across disparate systems and is distinct from aggregation patterns in macroparasites, and contains signatures of potential biological processes of amphibian-Bd systems. Our work lays a foundation to unite host-fungal dynamics under a common theoretical framework and inform future modeling approaches that may elucidate host-fungus interactions.
The Balanced Mind and its Intrinsic Neural Timescales in Advanced Meditators
Authors: Malipeddi Saketh , Sasidharan Arun , Venugopal Rahul , Ventura Bianca , Bauer Clemens Christian , P.N. Ravindra , Mehrotra Seema , John John P , Kutty Bindu M , Northoff Georg
Published: August 2024

A balanced mind, or equanimity, cultivated through meditation and other spiritual practices, is considered one of the highest mental states. Its core features include deidentification and non-duality. Despite its significance, its neural correlates remain unknown. To address this, we acquired 128-channel EEG data (n = 103) from advanced and novice meditators (from the Isha Yoga tradition) and controls during an internal attention (breath-watching) and an external attention task (visual-oddball paradigm). We calculated the auto-correlation window (ACW), a measure of brain’s intrinsic neural timescales (INTs) and assessed equanimity through self-report questionnaires. Advanced meditators showed higher levels of equanimity and shorter duration of INTs (shorter ACW) during breath-watching, indicating deidentification with mental contents. Furthermore, they demonstrated no significant differences in INTs between tasks, indicating non-dual awareness. Finally, shorter duration of INTs correlated with the participants’ subjective perceptions of equanimity. In conclusion, we show that the shorter duration of brain’s INT may serve as a neural marker of equanimity.
Transport of herbicides by PIN-FORMED auxin transporters
Authors: Schulz Lukas , Ung Kien Lam , Koutnik-Abele Sarah , Stokes David L , Pedersen Bjørn Panyella , Hammes Ulrich Z.
Published: August 2024

Auxins are a group of phytohormones that control plant growth and development1. Their crucial role in plant physiology has inspired development of potent synthetic auxins that can be used as herbicides2. Phenoxyacetic acid derivatives are a widely used group of auxin herbicides in agriculture and research. Despite their prevalence, the identity of the transporters required for distribution of these herbicides in plants is both poorly understood and the subject of controversial debate3,4. Here we show that PIN-FORMED auxin transporters transport a range of phenoxyacetic acid herbicides across the membrane and we characterize the molecular determinants of this process using a variety of different substrates as well as protein mutagenesis to control substrate specificity. Finally, we present Cryo-EM structures ofArabidopsis thalianaPIN8 with 2,4-dichlorophenoxyacetic acid (2,4-D) or 4-chlorophenoxyacetic acid (4-CPA) bound. These structures represent five key states from the transport cycle, allowing us to describe conformational changes associated with substrate binding and transport across the membrane. Overall, our results reveal that phenoxyacetic acid herbicides use the same export machinery as endogenous auxins and exemplify how transporter binding sites undergo transformations that dictate substrate specificity. These results enable development of novel synthetic auxins and for guiding precision breeding of herbicide resistant crop plants.
Genome-wide A→G and C→T Mutations Induced by Functional TadA Variants inEscherichia coli
Authors: Wang Hao , Dong Zhengxin , Shi Jingyi , Chen Lei , Sun Tao , Zhang Weiwen
Published: August 2024

The fusion expression of DNA replication-related proteins with nucleotide deaminase enzymes promotes random mutations in bacterial genomes, thereby increasing genetic diversity among population. Most previous studies have focused on cytosine deaminase, which produces only C→T mutations, significantly limiting the variety of mutation types. In this study, we developed a fusion expression system by combining DnaG (RNA primase) with adenine deaminase TadA-8e (DnaG-TadA) inEscherichia coli, which is capable of rapidly introducing A→G mutations into theE. coligenome, resulting in a 664-fold increase in terms of mutation rate. Additionally, we engineered a dual-functional TadA variant, TadAD, and then fused it with DnaG. This construct introduced both C→T and A→G mutations into theE. coligenome, with the mutation rate further increased by 370-fold upon co-expression with an uracil glycosylase inhibitor (DnaG-TadAD-UGI). We applied DnaG-TadA and DnaG-TadAD-UGI systems to the adaptive laboratory evolution for Cd2+and kanamycin resistance, achieving an 8.0 mM Cd2+and 200 μg/mL kanamycin tolerance within just 17 days and 132 hours, respectively. Compared to conventional evolution methods, the final tolerance levels were increased by 320% and 266%, respectively. Our work offers a novel strategy for random mutagenesis inE. coliand potentially other prokaryotic species.

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