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Quantitative assessment of lumbar dural mater pulsations using granger causality testing for spinal dynamics

Ethylene response factor SlERF.D6 promotes ripening in part through transcription factors SlDEAR2 and SlTCP12

Ripening is crucial for the development of fleshy fruits that release their seeds following consumption by frugivores and are important contributors to human health and nutritional security. Many genetic ripening regulators have been identified, especially in the model system tomato, yet more remain to be discovered and integrated into comprehensive regulatory models. Most tomato ripening genes have been studied in pericarp tissue, though recent evidence indicates that locule tissue is a site of early ripening-gene activities. Here, we identified and functionally characterized an Ethylene Response Factor (ERF) gene, SlERF.D6 , by investigating tomato transcriptome data throughout plant development, emphasizing genes elevated in the locule during fruit development and ripening. SlERF.D6 loss-of-function mutants resulting from CRISPR/Cas9 gene editing delayed ripening initiation and carotenoid accumulation in both pericarp and locule tissues. Transcriptome analysis of lines altered in SlERF.D6 expression revealed multiple classes of altered genes including ripening regulators, in addition to carotenoid, cell wall, and ethylene pathway genes, suggesting comprehensive ripening control. Distinct regulatory patterns in pericarp versus locule tissues were observed, indicating tissue-specific activity of this transcription factor (TF). Analysis of SlERF.D6 interaction with target promoters revealed an APETALA 2/ETHYLENE RESPONSE FACTOR (AP2/ERF) TF ( SlDEAR2 ) as a target of SlERF.D6. Furthermore, we show that a third TF gene, SlTCP12 , is a target of SlDEAR2, presenting a tricomponent module of ripening control residing in the larger SlERF.D6 regulatory network.

Ninth Annual Go Red for Women Issue

Development of a conceptual framework of sexual health for married elderly women: An exploratory mixed method study

Background Identifying elderly women’s sexual health demands based on their lived experience is essential since it leads to their sexual rights promotion. The present framework was designed to identify sexual demands, develop a reliable and valid questionnaire, and present it to policymakers. Methods This conceptual framework was designed in four phases using an exploratory sequential approach. The first phase included a review of related literature to identify elderly women’s sexual health demands. In the second phase, the qualitative phase, the participants will be interviewed to identify their sexual health demands. Data will be collected through in-depth semi-structured interviews until data saturation. In the third phase, a draft questionnaire will be provided using the data from the qualitative study and literature review to measure the sexual health demands of elderly women. Afterward, the face and content validity, as well as the construct and criterion validity, will be determined. The construct and criterion validity will be assessed using exploratory factor analysis and a cross-sectional study on elderly women, respectively. Finally, the reliability of the questionnaire will be determined. In the fourth phase, using the classical Delphi technique, the panel of experts will select the most important demands to present to policymakers. Results Based on a literature review conducted from October 20, 2023, to March 15, 2024, the demands were categorized into three main groups: “the elimination of ageist attitudes,” “the elimination of sexism,” and “the elimination of sexual retirement.” Other data and their integration with the literature review data to finalize the categories will be obtained after conducting qualitative interviews. Afterward, the questionnaire will be developed and psychometrically evaluated. Finally, the demands will be prioritized for policymakers. Conclusion According to the results, elderly women face social and cultural challenges in maintaining sexual health. Based on the presented methods, comprehensive and complete identification of demands in different cultures can facilitate sexual health planning.

Symmetry-based analysis after surgical treatment of zygomaticomaxillary complex fractures using intraoperative cone-beam computed tomography: a retrospective case-control study

Abstract Zygomaticomaxillary fractures are among the most common fractures of the facial skeleton. Open reduction and internal fixation require radiographic control. Three-dimensional radiographs provide superior information on actual distances. The study aims to quantify and evaluate intraoperative reduction control by cone-beam computed tomography. The retrospective case-control study evaluates three-dimensional radiographs through linear measurements of defined skeletal landmarks from the median sagittal plane for symmetry. The study group received open reduction and internal fixation for zygomaticomaxillary fractures, and the control group consisted of a population without pathology of the midfacial region. The study group showed the same degree of symmetry as the control group. The mean absolute distance of all landmarks was 1.5 ± 1.3 mm in the study group and 1.0 ± 0.9 mm in the control group. There was a statistically significant likelihood of the right side being further away from the midline than the left. The study showed adequate reduction results of zygomaticomaxillary fractures. Moreover, the same degree of symmetry was ascertained compared to a control group. Intraoperative cone-beam computed tomography serves as a valid tool to check for immediate reduction control during surgery for zygomaticomaxillary fractures.

Decoding resistance in the age of T6SS warfare

Hypertension in Pregnancy and Postpartum: Current Standards and Opportunities to Improve Care

Hypertension in pregnancy contributes substantially to maternal morbidity and mortality, persistent hypertension, and rehospitalization. Hypertensive disorders of pregnancy are also associated with a heightened risk of cardiovascular disease, and timely recognition and modification of associated risk factors is crucial in optimizing long-term maternal health. During pregnancy, there are expected physiologic alterations in blood pressure (BP); however, pathophysiologic alterations may also occur, leading to preeclampsia and gestational hypertension. The diagnosis and effective management of hypertension during pregnancy is essential to mitigate maternal risks, such as acute kidney injury, stroke, and heart failure, while balancing potential fetal risks, such as growth restriction and preterm birth due to altered uteroplacental perfusion. In the postpartum period, innovative and multidisciplinary care solutions that include postpartum maternal health clinics can help optimize short- and long-term care through enhanced BP management, screening of cardiovascular risk factors, and discussion of lifestyle modifications for cardiovascular disease prevention. As an adjunct to or distinct from postpartum clinics, home BP monitoring programs have been shown to improve BP ascertainment across diverse populations and to lower BP in the months after delivery. Because of concerns about pregnant patients being a vulnerable population for research, there is little evidence from trials examining the diagnosis and treatment of hypertension in pregnant and postpartum individuals. As a result, national and international guidelines differ in their recommendations, and more studies are needed to bolster future guidelines and establish best practices to achieve optimal cardiovascular health during and after pregnancy. Future research should focus on refining treatment thresholds and optimal BP range peripartum and postpartum and evaluating interventions to improve postpartum and long-term maternal cardiovascular outcomes that would advance evidence-based care and improve outcomes worldwide for people with hypertensive disorders of pregnancy.

The Cancer Tracking System (CATSystem): Study protocol of a randomized control trial to evaluate a systems level intervention for cervical cancer screening, treatment, referral and follow up in Kenya

Background Cervical cancer (CC) is preventable, yet remains a significant public health threat, particularly in Sub-Saharan Africa. Despite considerable awareness, screening rates for CC in Kenya are low and loss to follow-up following treatment for premalignant cervical lesions remains high. This study investigates the efficacy of the Cancer Tracking System (CATSystem), a web-based intervention, to improve CC screening and treatment retention. Methods A matched, cluster randomized controlled trial will be conducted in Kenyan government hospitals (n = 10) with five intervention and five standard-of-care (SOC) sites. The primary outcome is the proportion of women with a positive screen who receive appropriate treatment (onsite or referral). Secondary outcomes include CC screening uptake among all women and timeliness of treatment initiation. We will utilize mixed methods to assess intervention feasibility, acceptability, and cost-effectiveness. Discussion The CATSystem has the potential to improve CC care in Kenya by leveraging existing technology to address known barriers in the screening and treatment cascade. This study will provide valuable evidence for potential scale-up of the intervention.

N6-methyladenosine (m6A)-forming enzyme METTL3 controls UAF1 stability to promote inflammation in a model of colitis by stimulating NLRP3

Abstract Background The rising incidence of ulcerative colitis (UC) in China poses a noticeable health challenge. This study aimed to assess the pivotal role of USP1-associated factor 1 (UAF1) in colitis. UC was induced in male C57BL/6 mice using 2.0% dextran sulfate sodium (DSS). In an in vitro model, RAW264.7 cells were exposed to 200 ng/ml of LPS + ATP. UAF1 expression level was evaluated in colonic tissues, macrophages, and serum samples using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The study assessed weight, disease activity index (DAI) score, myeloperoxidase (MPO) activity, crypt length, inflammatory factors, and epithelial cell function in a mouse model of colitis treated with a UAF1 inhibitor. Microarray analysis identified potential UAF1 targets. Gene interference investigated NLR family pyrin domain containing 3 (NLRP3) involvement in UAF1-induced colitis inflammation. Immunoprecipitation, ubiquitination, and luciferase assays examined the effects of methyltransferase-like 3 (METTL3) methylation on the expression levels of NLRP3 and UAF1. UAF1 expression level was upregulated in colon tissues, RAW264.7 macrophages, and serum samples of colitis mice (P < 0.01). The UAF1 inhibitor (ML-323) enhanced weight and reduced DAI score in colitis mice (P < 0.01). It also decreased MPO activity and ulcer area, and restored crypt length (P < 0.01). UAF1 inhibitor improved epithelial cell function by suppressing NLRP3 activity (P < 0.01). UAF1 promoted inflammation in RAW264.7 macrophages via NLRP3 inflammasome induction (P < 0.01). UAF1 modulated NLRP3 protein expression, leading to reduced NLRP3 ubiquitination induced by LPS + ATP. The m6A-forming enzyme METTL3 enhanced UAF1 stability (P < 0.01) to facilitate UAF1 expression. The findings suggested that METTL3, as an m6A-forming enzyme, could regulate UAF1 mRNA, promoting inflammation in colitis through NLRP3 induction. Inhibiting UAF1 emerges as a potential therapeutic strategy for colitis.

Clinical evaluation of patterned dried plasma spot cards to support quantification of HIV viral load and reflexive genotyping

Quantifying viral load, a key indicator required to achieve control and elimination of the HIV epidemic, requires cell-free plasma or serum to ensure measurements are not biased by proviral DNA contained in infected CD4 T lymphocytes. Plasma separation cards (PSC) collect and preserve a dried specimen, which makes them practical solutions for decentralized sample collection and transport in limited-resource settings. However, physiological variations in hematocrit levels can introduce significant variability in the quality of plasma generated by commercial PSCs and can lead to inaccurate test results and clinical decisions. In addition to hematocrit-dependent sampling, the Roche PSC, a standard for dried plasma collection, is known to induce considerable hemolysis, which further impacts specimen quality, concordance with liquid plasma, and the overall benefit of microsampling. We address these gaps with a patterned dried plasma spot (pDPS) card, which generates plasma with improved hematocrit independence and minimal hemolysis. This study directly compares pDPS cards to the Roche PSC to measure HIV viral load. Analysis of viral load from 75 donors revealed strong agreement in sensitivity, specificity, overall accuracy, and viral load band placement between devices, with quantitative metrics suggesting improved performance for pDPS cards. In reflexive genotyping, remnant dried blood from pDPS cards exhibited greater success than Roche PSC in amplification and sequencing (71% vs. 62%) and detecting drug resistance mutations (63% vs. 42%). Based on this performance, pDPS cards can be versatile across multiple analytical platforms, integrate seamlessly into existing clinical laboratory workflows, and aid clinicians in making accurate treatment decisions.

Study on R&D result subsidy strategies for PEV enterprises based on heterogeneous consumer technology thresholds and preferences under anxiety issues

Many governments worldwide hoped to stimulate Pure Electric Vehicle(PEV) enterprises’ R&D and sales through R&D result subsidy policies, but the anxiety issues significantly reduced PEV sales and weakened the policy effectiveness. To achieve better incentive effects, considering the impact of anxiety issues on subsidy strategies is necessary. As anxiety problems stem from typical behavior characteristics of PEV consumers——consumer technology thresholds, reasonable study should understand them and quantify their impact from the perspective of consumer technology thresholds. Therefore, it constructs a sequential game model among the government, the PEV company, and consumers with two dimensions of heterogeneous behavior characteristics——technology thresholds and preferences. It also determines the optimal R&D result subsidy strategies and analyzes the impact of the technology thresholds and preferences on them. It shows that the government should provide subsidies except for PEV enterprises with R&D efficiency in the higher range, and its optimal strategies must consider consumer technology threshold and preference conditions. The lower the technology thresholds of PEV consumers, the lower the optimal subsidy ratio until the technology level of the enterprise is already high enough, and there is no need for subsidies. Higher consumer technology preferences of PEV consumers will achieve the same effect. The numerical simulation shows that compared to other models, the model considering PEV consumer technology thresholds can optimize the subsidy ratio and achieve better incentive effects.

Retrospective analysis of clinical data from 171 low-income patients with hemophilia in Shandong Province

Thermoelastic twisting–assisted crystal jumping based on a self-healing molecular crystal

Adaptive crystals have attracted significant attention from solid-state chemists and crystal engineers for their promising applications in memories, capacitors, sensors, and actuators. Among them, thermosalient crystals are particularly favored thanks to their efficient energy conversions and rapid responses. However, the mechanisms for the mechanical responses of thermosalient crystals remain largely unclear. Herein we demonstrate that thermosalient effects of molecular crystals could be driven by thermoelastic twisting behaviors. The crystal, based on a model compound with rigid dibenzothiophene sulfone planes and flexible ethoxy chains, can spontaneously self-heal from mechanical fractures. Upon heating, the crystal undergoes remarkable thermosalient behaviors driven by a distinctive left- or right-handed twisting. This thermoelastic twisting converts thermal energy into elastic potential energy, which is further released as kinetic energy upon untwisting to drive the crystal jump. Our demonstration on thermoelastic twisting–induced crystal jumping offers a different perspective on the origins of thermosalient crystals and could provide inspiration for future engineering and application of dynamic molecular crystals.

Persistent advanced HIV disease in rural KwaZulu-Natal, South Africa: Trends, characteristics, and the urgent need for targeted interventions

Background Advanced HIV disease (AHD) remains a persistent public health challenge. Data regarding the burden, characteristics and predictors of AHD is scarce specifically for rural settings of sub-Saharan Africa. This study aimed to describe trends in annual CD4 count distribution and to characterise adult persons living with HIV (PLWH) on ART who have AHD in rural KwaZulu-Natal, South Africa. Methods A retrospective cohort design of annual CD4 count distribution was conducted among antiretroviral therapy (ART) patients aged 18 years and older. We used routinely collected data from adults receiving ART in Eshowe and Mbongolwane areas in KwaZulu-Natal, South Africa, between January 1, 2008, and June 30, 2021. Fine-Greys competing risks regression with proportional sub-distribution hazard models was used to determine factors associated with time to CD4 recovery. Results A total of 34,729 patients were included of which 68.5% were females. The median age of the study sample was 33.5 years (interquartile range [IQR] 27–41 years), and the median CD4 count was 277 cells/μL (IQR, 149–452 cells/μL). The proportion of patients entering care with AHD declined over time from 62% in 2008 to 20% in 2021. Across all periods, those entering care with AHD were more likely to be men when compared to women (Relative risk [RR] 1.49; 95% 1.33–1.67). In addition, the proportion of patients with AHD who were ART-experienced increased from 4% in 2008 to 63% in 2021. Among ART-experienced, men were more likely to present with AHD compared to women (RR 1.79; 95% CI 1.52–2.11). Among those with AHD, the cumulative incidence of CD4 recovery to > 350 cells/μL was 3.21 (95% CI 3.13–3.29) per 100 adult-years follow-up time. Conclusion Over time fewer patients with AHD are entering care in KwaZulu-Natal, South Africa. However, the proportion of PLWH entering care with AHD remains consistently high, affecting 1 in 4 PLWH accessing HIV services. In addition, there is an increasing number of ART-experienced patients with AHD. Implementation of male-friendly services, combined with intensified adherence support and re-engagement initiatives should be considered to reduce mortality risk for PLWH in rural regions in South Africa.

The indirect L-valleys splitting inductive optical gain variation of $$\hbox {Ge}_{1-x}\hbox {Sn}_{x}$$ nanowires caused by [110] direction uniaxial stress

Machine learning–enhanced surface-enhanced spectroscopic detection of polycyclic aromatic hydrocarbons in the human placenta

The detection and identification of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, polycyclic aromatic compounds (PACs), are essential for environmental and health monitoring, for assessing toxicological exposure and their associated health risks. PAHs/PACs are the most dangerous chemicals found in tobacco smoke, and cigarette use during pregnancy can convey these molecules to the developing fetus through the placenta. This exposure is associated with many negative health outcomes, from premature birth to sudden infant death syndrome and adverse neurodevelopmental disorders. This study demonstrates the use of surface-enhanced Raman and surface-enhanced infrared absorption spectroscopies for direct detection of PAHs/PACs in human placental tissue. We applied two spectroscopy-informed machine learning algorithms, Characteristic Peak Extraction (CaPE) and Characteristic Peak Similarity (CaPSim), to identify the specific PAHs and PACs present in the placenta of women who smoked tobacco cigarettes in pregnancy compared to spectra of the placenta from self-reported nonsmokers. CaPE and CaPSim analysis enabled a clear distinction between these two groups. Independent verification was accomplished by detecting PAH-DNA and PAC-DNA adducts in the smoking group by means of a 32 P-postlabeling assay. These findings highlight the effectiveness of combining surface-enhanced spectroscopies with informed ML analysis for the streamlined detection of hazardous environmental compounds in human tissues, suggesting broader applications in clinical diagnostics and public health surveillance.

Genetic evidence for amlodipine’s protective role in gastroesophageal reflux disease: A focus on CACNB2

Objective This study aims to elucidate the causal relationship between genetically predicted amlodipine use and the risk of gastroesophageal reflux disease (GERD) using a bidirectional Mendelian Randomization (MR) approach and to explore the underlying genetic and molecular mechanisms through functional enrichment analysis and the construction of a competing endogenous RNA (ceRNA) network. Methods Publicly available GWAS datasets from the Neale Lab consortium were used, including data on amlodipine (13,693 cases, 323,466 controls) and GERD (14,316 cases, 322,843 controls). Genome-wide significant SNPs were selected as instrumental variables and clustered by linkage disequilibrium. MR analysis was conducted using R software with all five methods. Sensitivity analyses assessed pleiotropy and heterogeneity. Drug target genes were analyzed using GO and KEGG pathways. GeneMANIA was used for network visualization, and a ceRNA network was constructed with Cytoscape. Differential gene expression analysis on GERD-related datasets from GEO validated the findings. Results The MR analysis indicated a significant negative association between genetically predicted amlodipine use and GERD risk (IVW OR = 0.872, 95% CI = 0.812–0.937, P = 0.0002). Sensitivity analyses confirmed the robustness of these findings, showing no evidence of pleiotropy or heterogeneity. The enrichment analysis identified key biological processes and pathways involving calcium ion transport and signaling. The ceRNA network highlighted core targets such as CACNB2, which were further validated by differential expression analysis intersecting drug target genes with GERD-related gene expression changes. Conclusion This study provides robust evidence of a protective effect of amlodipine against GERD, supported by genetic and molecular analyses. The findings suggest that calcium channel blockers like amlodipine could be repurposed for GERD treatment. The identification of CACNB2 and other core targets in the ceRNA network offers novel insights into the pathophysiology of GERD and potential therapeutic targets, paving the way for personalized medicine approaches to improve patient outcomes.

In vitro protein expression profile of cultivated muscle cells from Labeo rohita

Dynamic changes in histone lysine lactylation during meiosis prophase I in mouse spermatogenesis

Male germ cells, which are responsible for producing millions of genetically diverse sperm through meiosis in the testis, rely on lactate as their central energy metabolite. Recent study has revealed that lactate induces epigenetic modification in cells through histone lysine lactylation. Here, we report dynamic histone lactylation at histone H4-lysine 5 (K5), -K8, and -K12 during meiosis prophase I in mouse spermatogenesis. By profiling the genome-wide occupancy of histone H4-K8 lactylation (H4K8la), which peaks at zygotene, our data show that H4K8la mark is observed at the promoters of genes exhibiting active expression with Gene Ontology functions enriched for meiosis. Notably, our data also demonstrate that H4K8la is closely associated with recombination hotspots, where machinery involved in the processing DNA double-stranded breaks, such as SPO11, DMC1, RAD51, and RPA2, is engaged. In addition, H4K8la was also detected at the meiosis-specific cohesion sites (marked by RAD21L and REC8) flanking the recombination hotspots. Functionally, our data show that lactate induces upregulation of key meiotic genes through H4K8la modifications. Additionally, H4K8la shows colocalization and interaction with PRDM9 at recombination hotspots. Finally, our data show that HBO1, a lactyltransferase, is highly expressed in meiotic germ cells. In vitro lactylation assays reveal that HBO1 induces H4K8la, and pharmacological inhibition of HBO1 in mice reduces H4K8la levels and disrupts meiosis. Collectively, our findings suggest that histone lactylation serves as an epigenetic mechanism that is involved in meiotic gene expression and recombination in male germ cells during spermatogenesis.

Transcriptome analyses reveal differences in the response to temperature in Florida and Northern largemouth bass (Micropterus spp.) during early life stages

Temperature is one of the most relevant factors influencing the development of aquatic species, making it a key parameter to consider for aquaculture. Largemouth bass (LMB; Micropterus spp.) are highly relevant for human consumption and sport fishing, representing one of North America’s most important freshwater fisheries. Yet, questions remain on how LMB raised in recirculating aquaculture systems (RAS) respond to different temperatures. The main objective of this study was to determine the impact of thermal rearing conditions (21°C, 24°C, and 27°C) on gene expression of Florida and Northern LMB larvae at 8- and 28-days post hatch (DPH). Using de novo transcriptomes as a reference, our results suggest that gene expression differences for Florida LMB were mostly associated with temperature, while differences for Northern LMB were controlled by temperature and developmental stage. In general, both lineages showed activation of molecular pathways associated growth, such as development of muscle, nervous system, and vascular system. There were molecular signatures of stress with warming as well, including immune function, apoptosis, regulation of inflammation, and heat shock proteins. Florida LMB showed large differences between temperatures at both stages, while differences were much larger for Northern LMB at 28 DPH, specifically for individuals reared at 27°C. The results from this study are in line with previous phenotypic studies that indicated faster growth at warmer temperatures and better performance of Northern LMB raised in RAS. Overall, this study exemplifies how controlling developmental temperatures during the critical early life stages can be essential to guarantee the success of commercial hatchery production techniques.