Significant Decline Research Articles

Functional Progression after Dose Suspension or Discontinuation of Nintedanib in Idiopathic Pulmonary Fibrosis: A Real-Life Multicentre Study.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with rapidly progressive evolution and an unfavorable outcome. Nintedanib (NTD) is an antifibrotic drug that has been shown to be effective in slowing down the progression of the disease. The aim of our study was to examine the efficacy, especially in terms of the functional decline, and the safety profile of NTD in patients treated with the recommended dose and subjects who reduced or suspended the therapy due to the occurrence of adverse reactions. We conducted a real-life retrospective study based on the experience of NTD use in two centers between 2015 and 2022. Clinical data were evaluated at baseline, at 6 and 12 months after the NTD introduction in the whole population and in subgroups of patients who continued the full-dose treatment, at a reduced dosage, and at the discontinuation of treatment. The following data were recorded: the demographic features, IPF clinical features, NTD therapeutic dosage, tolerability and adverse events, pulmonary function tests (PFTs), the duration of treatment upon discontinuation, and the causes of interruption. There were 54 IPF patients who were included (29.6% females, with a median (IQR) age at baseline of 75 (69.0-79.0) years). Twelve months after the introduction of the NTD therapy, 20 (37%) patients were still taking the full dose, 11 (20.4%) had reduced it to 200 mg daily, and 15 (27.8%) had stopped treatment. Gastrointestinal intolerance predominantly led to the dose reduction (13.0%) and treatment cessation (20.4%). There were two deaths within the initial 6 months (3.7%) and seven (13.0%) within 12 months. Compared to the baseline, the results of the PFTs remained stable at 6 and 12 months for the entire NTD-treated population, except for a significant decline in the DLCO (% predicted value) at both 6 (38.0 ± 17.8 vs. 43.0 ± 26.0; p = 0.041) and 12 months (41.5 ± 15.3 vs. 44.0 ± 26.8; p = 0.048). The patients who continued treatment at the full dose or a reduced dosage showed no significant differences in the FVC and the DLCO at 12 months. Conversely, those discontinuing the NTD exhibited a statistically significant decline in the FVC (% predicted value) at 12 months compared to the baseline (55.0 ± 13.5 vs. 70.0 ± 23.0; p = 0.035). This study highlights the functional decline of the FVC at 12 months after the NTD initiation among patients discontinuing therapy but not among those reducing their dosage.

Experiment study on flexural performance of steel concrete composite beams under salt freeze-thaw cycles in negative moment sections

Bridge structures in cold climates face significant challenges due to freeze-thaw cycles and salt-induced corrosion. This study investigates the degradation mechanisms of the negative bending behavior of steel-concrete composite beams using normal concrete (NC) and ultra-high performance concrete (UHPC) under salt freeze-thaw cycles (SFTC), considering the impact of different stud arrangements. The results indicate that UHPC significantly enhances the cracking performance in the negative bending region of the composite beams and demonstrates high resistance to SFTC. Before undergoing SFTC, the cracking moment of the UHPC beams increased by an average of 210.5%, and stiffness by 37.3%, compared to the NC composite beams. After 150 SFTCs, the NC beams showed a significant decline in performance, with a 62.1% reduction in cracking moment, a 6.2% decrease in load-carrying capacity, and a 5.6% reduction in stiffness. In contrast, the flexural performance of the UHPC beams was almost unaffected, with only a 17.5% reduction in cracking load. Moreover, beams with a double-row stud configuration exhibited better negative bending resistance compared to those with a single-row stud configuration. Based on experimental results and data from reference, a reasonable formula for predicting the composite beams under the effect of SFTCs was proposed and proved to have satisfactory accuracy.

Co-treatment of silymarin and cisplatin inhibited cell proliferation, induced apoptosis in ovarian cancer.

Ovarian cancer is one of the most lethal gynecological cancers among women worldwide. Cisplatin (Cis) is an effective chemotherapeutic agent used to treat several types of cancer. Silymarin (SLM) is an extract of medicinal plant Silybum marianum (milk thistle) with anti-inflammatory, anti-angiogenesis, antioxidant, and anticancer properties used alone or in combination with other drugs. This study aimed to explore the effects of co-treatment with SLM and Cis on A2780 human ovarian cancer cell lines. In this study, A2780 cells were treated with various concentrations of SLM and Cis, separately and in combination. Cell cytotoxicity, scratch, clonogenic, and flow-cytometry assays were accomplished to estimate cell viability, migration, colony formation, and apoptosis, respectively. Real-time PCR was utilized to determine the expression levels of miR-155 and miR-27a. SLM significantly reduced the proliferation of A2780 cells in a concentration- and time-dependent manner. Combination treatment with SLM and Cis was more potent than either single treatment in reducing viability, suppressing migration, inhibiting colony formation, and promoting the induction of apoptosis. Additionally, gene expression analysis revealed a significant decline in the expression levels of miR-155 and miR-27a in response to all separate and combined treatments, and co-treatment was more effective than individual treatments in altering miRNAs expression. Based on our findings, SLM boosts the anticancer activity of Cis and mitigates its side effects. Thus, the co-treatment of SLM and Cis can be proposed as a promising therapeutic strategy for further investigation.

Sustainability in Industry, Innovation and Infrastructure: A MCDM Based Performance Evaluation of European Union and Türkiye for Sustainable Development Goal 9 (SDG 9)

Purpose: The aim of this study is to perform two distinct cross-country evaluations including European Union (EU) countries and Türkiye, focusing on Sustainable Development Goal 9 (SDG 9): Industry, innovation and infrastructure. The study aims to obtain rankings that display the relative standings of countries and identify areas for potential enhancement.
 Methodology: An integrated objective criteria weighting, VIKOR, and MAIRCA based Multi-Criteria Decision Making (MCDM) approach has been employed.
 Findings: Based on the first analysis, high speed internet coverage (HSI) and the share of rail and inland waterways in inland freight transport (SRI) were prominent criteria, and in the MCDM analysis, Sweden displayed the highest performance, while Greece and Croatia showed the lowest performance. In the second analysis, which included Türkiye, tertiary educational attainment (TEA) criteria stood out; while, Sweden maintained its leading position. Türkiye initially had poor performance in the early years but later improved, reaching a mid-level position among 26 countries by 2020. However, a significant decline in performance was observed in the last two years. In addition, during the handled period Türkiye witnessed a decline in both the number of patent applications and the share of buses and trains in inland passenger transport. Thereby, novel policies and incentives could be formulated to overcome these issues.
 Originality: Two distinct cross-country analyses were conducted in accordance with the SDG 9 by adopting the most recent data and an integrated methodology. Within this context, EU countries were compared both among themselves and with Türkiye, and valuable findings were presented.

Effects of Serum Estradiol on Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Lipid Profiles in Women Undergoing In Vitro Fertilization.

The mechanisms underlying the impact of estradiol (E2) on low-density lipoprotein cholesterol (LDL-C) levels are not completely understood, although a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) has been proposed. We aimed to investigate the association between levels of E2, PCSK9, and lipid parameters in premenopausal women undergoing in vitro fertilization (IVF). Healthy women undergoing IVF in the Department of Obstetrics and Gynecology of the University General Hospital of Ioannina were recruited. Their levels of E2, PCSK9, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides (TGs) were measured 10 days after ovarian depression (E2min) and 7 days after ovarian stimulation (E2max). We included 34 consecutive women of median age 38 (interquartile range 26-46) years who underwent a full IVF cycle. As expected, E2 levels increased by 329.6% from E2min to E2max (108 [47-346] to 464 [241-2471] pg/mL, p < 0.05). During the same time, serum PCSK9 levels decreased by 30.8% (245 ± 80 to 170 ± 64 ng/mL, p < 0.05). TC, LDL-C, and TGs decreased by 0.4%, 3.8%, and 2.2%, respectively, while HDL-C levels increased by 5.3% (all p = NS). The rise in endogenous E2 during an IVF cycle was related with a significant decline in serum PCSK9 levels, but no significant change in plasma lipids during a 7-day period.

The Relationship between Time, Race, and Estrogen Receptor Alpha in Estradiol-Induced Dermal Fibrosis.

In the skin, estradiol (E2) promotes profibrotic and proinflammatory cytokines, contributing to extracellular matrix (ECM) deposition. However, the magnitude of the response differs. Using the human skin organ culture model, we evaluated donor characteristics and correlations that contribute to E2-induced interleukin-6 (IL-6), transforming growth factor beta 1 and 2 (TGFB1 and TGFB2), collagen IA2 (Col IA2), collagen IIIA1 (Col IIIA1), and fibronectin (FN) expressions. In vehicle- and E2-treated dermal skin tissue transcripts, we confirm differences in the magnitude; however, there were positive correlations between profibrotic mediators and ECM components 48 h after E2 treatment. Also, positive correlations exist between baseline and E2-induced TGFB1, IL-6, Col IIIA1, and FN transcripts. Since estrogen receptor alpha (ERA) can propagate E2's signal, we measured and detected differences in its baseline and fold change transcript levels, with a significant decline in baseline levels 48 h after incubation and an increase 48 h after E2 treatment. There was a trend to higher transcript levels in African American donors 24 h earlier. Finally, E2-induced ERA transcript levels negatively correlated with its own baseline levels and positively correlated with FN, TGFB1, and Col IA2 transcript levels. Therefore, our data suggest ERA, E2 exposure time, and race/ethnicity contribute to E2-induced dermal fibrosis.

Decreased microbial phylogenetic diversity and community stability due to less bioavailable carbon and greater oxygen supply in Mollisols along a cultivation chronosequence

Soil microorganisms support multiple agroecosystem functions, but responses of the microbiome to prolonged agricultural land-use and underlying mechanisms remain poorly understood. In this study, upland soils in the Mollisol region of Northeast China were selected along a 100-year cultivation chronosequence to examine the effects of intensive agriculture on the diversity, composition and co-occurrence network of bacterial and fungal communities. To elucidate the determinants driving the dynamics and interactions of microbial communities, the researchers quantified the functional groups and bioavailable fractions of soil organic carbon, and estimated the microenvironments including soil texture and oxygen availability. Our findings revealed that fungal diversity and community stability decreased over cultivation time, while that of bacteria showed a less significant decline. The increased oxygen availability and decreased soil carbon supply, particularly polyphenols, jointly drove the dynamics in the composition and stability of the microbial communities. Crucially, these microbial responses were significantly regulated by interspecific associations. Phylotypes showing stronger responses to changes in oxygen availability and carbon supply demonstrated a higher level of connectivity within co-occurrence networks, signifying their potential role as pivotal “hubs” in transmitting the environmental influences across the entire community via interspecific associations. Moreover, the decline in fungal diversity over longer cultivation periods could liberate more survival niches for bacterial species through fungi-bacteria associations, thereby bolstering the stability of the bacterial community. Overall, this study accentuates the pivotal role of trophic associations in facilitating the oxygen and carbon-induced succession of belowground microbiota in long-term cultivated Mollisols. In view of the agricultural intensification propelled by the increasing demand for crop production, these findings suggest strategies integrating improvements in soil structure and carbon with microbial processes to ensure the sustainability of agroecosystem functions.

Cellular behavior and extracellular matrix turnover in bovine annulus fibrosus cells under hydrostatic pressure and deviatoric strain.

Intervertebral disc herniation is a common spinal disorder that is often treated with discectomy when conservative measures fail. To devise therapeutic strategies for tears in the annulus fibrosus (AF), the regenerative capability of AF cells under spinal loading needs to be addressed. We hypothesized that the compressive loading associated with deformation in AF cells reduces synthetic and degradative activities in extracellular matrix and cell proliferation. We evaluated expression of key matrix molecules and cell proliferation by RT-PCR and immunohistochemistry by inner and outer bovine AF cells incubated under hydrostatic pressure (HP), arc-bending strain (Strain), and combined HP and Strain (HP/Strain) mimicking spinal loading. Inner AF cells showed significantly increased levels of aggrecan core protein, chondroitin sulfate N-acetylgalactosaminyltransferase-1, and tissue inhibitor of metalloproteinases-2 by 6 days under HP (p < 0.05), with a tendency toward increased matrix metalloproteinase-13. Outer AF cells demonstrated a significant decline in collagen type-2 under Strain and HP/Strain (p < 0.05) and a tendency toward suppression of collagen type-1 and elastin expression compared to HP and unloaded control. On the other hand, proliferating cell nucleus antigen increased significantly under Strain and HP/Strain in inner AF and declined under unloaded and HP in outer AF (p < 0.05). Immunohistology findings supported reductions in gene expressions of matrix molecules. Thus, changes in HP/Strain in AF appear to diminish synthetic and degradative activities while increasing cell proliferation. To promote regeneration, continuous overloading should be avoided, as it converts the synthetic activity to a state in which tissue repair is limited.

Effect and Mechanism of LIN28 on Ferroptosis in Mg2+-free Rat Hippocampal Neuron Model of Epilepsy.

Studies have demonstrated that LIN28 is expressed in the CNS and may exert protective effects on neurons. However, it remains unknown whether LIN28 regulates ferroptosis in the context of epilepsy. In this study, we established an epilepsy model by culturing hippocampal neurons from rats in a magnesium-free (Mg2+-free) medium. In Mg2+-depleted conditions, hippocampal neurons exhibited reduced LIN28 expression, heightened miR-142-5p expression, decreased glutathione peroxidase (GPX) activity and expression, elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in a significant decline in cell viability and an increase in ferroptosis. Conversely, overexpression of LIN28 reversed these trends in the mentioned indices. Altogether, this study reveals that LIN28 may exert neuroprotective effects by inhibiting the miR-142-5p expression and suppressing ferroptosis in hippocampal neurons induced by Mg2+-free via increasing GPX4 expression.

Examining human-wildlife conflict and management strategies in Indian protected areas: evidence from Jim Corbett Tiger Reserve

ABSTRACT The study examines the trends and patterns of human-wildlife conflict and explores stakeholders’ perceptions toward management strategies in the Jim Corbett Tiger Reserve, India. The study used a mixed “methods” research approach. Human-wildlife conflict quantitative data was analyzed using a trend line approach. Grounded Theory and thematic analysis were used to analyze local households (n = 150), park employees (n = 20), and eco-development committees (n = 10) interviews content. The results revealed a significant decline in human casualties, cattle depredation, and crop damage, possibly attributed to strategies like awareness programs, electric fencing, and alternative livelihoods. The study found no significant evidence of retaliatory wildlife killing by locals. Although human-wildlife conflict has declined significantly due to existing management strategies, the thematic analysis highlights serious challenges, including inadequate funding, insufficient compensation, and limited local participation in alternative livelihoods. These challenges need to be addressed urgently for the sustainable management of conflict.

Phosphorus Availability and Uptake following a Maize-Pigeon Pea Rotation under Conservation Agriculture

Soils on many smallholder farms in Southern Africa are severely depleted in plant nutrients, in particular phosphorus (P), following years of maize monocropping with little or no fertilizer input. Past studies suggest that pigeon pea (Cajanus cajan (L.) Millsp.) may increase plant-available P. Pigeon pea is not a common crop in much of Southern Africa, and the effect of locally grown pigeon pea varieties on plant-available P is unknown. We assessed the changes in plant-available P after growing pigeon pea varieties MPPV-2, MPPV-3, and Babati White in Zambia, viz. Lixisols of Choma and Mkushi, Acrisols of Chipata and Kasama, and Arenosols of Kaoma. The selected soils were not fertilized. Baseline soils (0–20 cm), sampled after long-term maize monocropping and soils from the same fields after growing pigeon pea were collected from field trials in Kaoma, Chipata, Choma, and Mkushi and analyzed for plant-available P. Further, a greenhouse study was conducted with soils from Kasama, Choma, Kaoma, and Chipata, under which soil P was determined before and after growing pigeon pea, soybean (Dina), and maize (SC 419) without fertilizer addition. Pigeon pea under field studies had no significant (p &gt; 0.05) effect on plant-available P in Choma, Kaoma, and Chipata. In Mkushi, pigeon pea cropping resulted in a 47.5% significant decline (p ≤ 0.05) in plant-available P, amounting to a loss of 11.2 kg ha−1. The greenhouse study showed a significant decline (p ≤ 0.001) in plant-available P after seven weeks of maize growth, while there was no significant (p &gt; 0.05) effect on plant-available P after soybean and pigeon pea cropping. The latter was primarily due to the significantly higher P uptake associated with larger biomass production of maize after seven weeks in the greenhouse. During the initial seven weeks, pigeon pea biomass had significantly higher P concentrations than maize. Thus, P deficiency symptoms were exhibited in maize, while pigeon pea appeared healthy. However, mobilized P, calculated as the sum of plant P and soil P after cropping minus soil P before planting, was significantly lower (p ≤ 0.01) in pigeon pea compared to soybean and maize. Synthesizing field and greenhouse experiments suggests that there is a low net decline of plant-available P from soils after pigeon pea cropping. Therefore, rotation with these pigeon pea varieties could be beneficial to resource-poor farmers due to low P removal and its ability to grow in P-deficient soil.

Bayesian joint longitudinal models for assessing the exploitation rates of sardine stock in the Mediterranean Sea

AbstractThe European sardine is a pelagic species of great ecological importance for the conservation of the Mediterranean Sea as well as economic importance for the Mediterranean countries. Its fishing has suffered a significant decline in recent years due to various economic, cultural and ecological reasons. This paper focuses on the evolution of sardine catches in the Mediterranean Sea from 1985 to 2018 according to the fishing Mediterranean country and the type of fishing practised, artisanal and industrial. We propose three Bayesian longitudinal linear mixed models to assess differences in the temporal evolution of artisanal and industrial fisheries between and within countries. Overall results confirm that Mediterranean fishery time series are highly diverse along their dynamics and this heterogeneity is persistent throughout the time. Furthermore, our results highlight a positive correlation between artisanal and industrial fishing. Finally, the study observes a consistent decreasing time trend in the quantity of fish landings. Although the causes of this feature could be also linked to economic motivations (such as a reduction in demand or the reorientation of fleets towards more commercially beneficial species), it may indicate a potential risk to the stock of this species in the Mediterranean Sea.

Main soil microbial groups assessed by phospholipid fatty acid analysis of temperate alley agroforestry systems on crop- and grassland

The phospholipid fatty acid (PLFA) composition of soils was analysed at three poplar-based silvo-arable systems and at one willow-based silvo-grassland alley agroforestry system in Central Germany. The objective was to analyse tree row effects on the PLFA composition of main fungal and main bacterial groups. The fungal groups were BAM (Basidiomycota + Ascomycota + Mucoromycota) and AMF (Arbuscular Mycorrhizal Fungi). The bacterial groups were Gram-negative, Firmicutes, and Actinobacteria. The total PLFA content varied between 53 and 170 nmol g−1 soil. Total PLFA and microbial biomass carbon (MBC) showed a strong linear relationship, which resulted in a mean MBC/total PLFA ratio of 4.2 μg nmol−1. AMF contributed on average 4 mol% and the fungal BAM group 10 % to total PLFA. Gram-negative bacteria contributed on average 37 mol%, Firmicutes 23 mol%, and Actinobacteria 6 mol% to total PLFA. The presence of poplar or willow trees increased the mean total PLFA content in comparison with the alleyways by 30 %. Especially the mean contribution of fungal PLFA to total PLFA showed a significant +7.0 mol% increase in the tree row compared with the alleyways, exclusively caused by the BAM group (+7.6 mol%), whereas the contribution of the AMF PLFA linearly decreased from the middle of the alleyway to the tree row at all sites. Within the alleyways, the Gram-negative/Firmicutes PLFA ratio showed a significant decline from the 1 m up to the 24 m distance samples at sites Dornburg and Forst. Despite a decrease of AMF in tree rows, agroforestry tree rows led to a rapid increase in fungi, most likely due to the promotion of ecto-mycorrhizal fungi.

Iodine Intake Trends in United States Girls and Women between 2011 and 2020

BackgroundUsual intakes of iodine in United States girls and women, including pregnant and lactating women have not been adequately studied. Adequate intake of iodine is critical for neurodevelopment of girls, thyroid functions, and reproductive health of women. ObjectivesThis study aimed to examine the adequacy and trends of iodine intake of United States girls and women between 2011 and 2020. MethodsWe mapped the sources of United States girls and women’s iodine intake from the 29 food groups between 2011 and 2020 using United States Department of Agriculture’s iodine data release 2. The total food intakes from 2 d of dietary recall of the United States National Health and Nutritional Examination Survey and estimated iodine concentrations of the food groups were used to calculate the usual iodine intakes of female participants. Trends of usual intakes, urinary iodine concentrations (UIC), and estimated intake adequacy were calculated. ResultsMedian usual intakes of iodine estimated from diet and supplements and UIC of United States girls and nonpregnant, nonlactating women declined between 2011 and 2020 in all 3 age groups: ≤14 y, 15–49 y old, and ≥50 y. Median usual intakes of iodine for pregnant and lactating United States women declined as well. Inadequacy levels of usual iodine intake were 9.9% for nonpregnant, nonlactating women of reproductive age 15–49 y old, 40.3% for lactating, and 10.2% for pregnant women in the 2017–2020 period. Intake insufficiencies estimated from UIC were 48.8%, 63.2%, and 31.3% for nonpregnant, nonlactating women of reproductive age 15–49 y old, pregnant and lactating women, respectively, in the 2017–2020 period. A significant decline in milk consumption might be one of the major contributors to the dietary iodine decline in United States women. ConclusionsIodine intake of United States girls and women were on the decline between 2011 and 2020 and the increased inadequacy of iodine intake deserves public health attention.

VSIG4 inhibits RANKL-induced osteoclastogenesis by enhancing Nrf2-dependent antioxidant response against reactive oxygen species production

Osteoporosis is a prevalent systemic skeletal disorder, particularly affecting postmenopausal women, primarily due to excessive production and activation of osteoclasts. However, the current anti-osteoporotic drugs utilized in clinical practice may lead to certain side effects. Therefore, it is necessary to further unravel the potential mechanisms regulating the osteoclast differentiation and to identify novel targets for osteoporosis treatment. This study revealed the most significant decline in VSIG4 expression among the VSIG family members. VSIG4 overexpression significantly inhibited RANKL-induced osteoclastogenesis and bone resorption function. Mechanistically, both western blot and immunofluorescence assay results demonstrated that VSIG4 overexpression attenuated the expression of osteoclast marker genes and dampened the activation of MAPK and NF-κB signaling pathways. Furthermore, VSIG4 overexpression could inhibit the generation of reactive oxygen species (ROS) and stimulate the expression of Nrf2 along with its downstream antioxidant enzymes via interaction with Keap1. Notably, a potent Nrf2 inhibitor, ML385, could reverse the inhibitory effect of VSIG4 on osteoclast differentiation. In line with these findings, VSIG4 overexpression also mitigated bone loss induced by OVX and attenuated the activation of osteoclasts in vivo. In conclusion, our results suggest that VSIG4 holds promise as a novel target for addressing postmenopausal osteoporosis. This is achieved by suppressing osteoclast formation via enhancing Nrf2-dependent antioxidant response against reactive oxygen species production.

The prevalence of gestational syphilis in Malawi between 2014 and 2022: spatiotemporal modeling of population-level factors.

Mother-to-child transmission of syphilis remains high especially in the WHO AFRO region with a prevalence of 1.62%, resulting in a congenital syphilis rate of 1,119 per 100,000 live births. Elimination efforts can be supported by an understanding of the spatial and temporal changes in disease over time, which can identify priority areas for targeted interventions aimed at reducing transmission. We collated routine surveillance data from health facilities and covariate data from demographic and health surveys conducted in Malawi between 2014 and 2022. We fitted a Bayesian hierarchical mixed model with spatial and temporally structured random effects to model the district-level monthly counts of maternal syphilis notifications as a function of individual- and district-level predictors. We then generated district-level spatiotemporally explicit risk profiles to estimate the effect of individual- and district-level covariates on maternal syphilis notifications and to identify hotspot areas. Overall, the national prevalence of maternal syphilis increased from 0.28% (95% CI: 0.27-0.29%) in 2014 to peaking in 2021 at 1.92% (95% CI: 1.89-1.96%). Between 2020 and 2022, there was a decline in prevalence, with the most significant decline seen in Zomba District (1.40, 95% CI: 1.12-1.66%). In regression models, a one percentage point increase in district-level antenatal HIV prevalence was associated with increased maternal syphilis (prevalence ratio [PR]: 1.15, 95% credible interval [CrI]: 1.10-1.21). There was also an increased prevalence of maternal syphilis associated with an increased district-level mean number of sex partners (PR: 1.05, 95% CrI: 0.80-1.37). The number of districts with a high prevalence of maternal syphilis also increased between 2014 and 2022, especially in the southern region, where most had a high probability (approaching 100%) of having high maternal syphilis (defined as relative risk >1 compared to the standard population of women aged 15-49 years) in 2022. Maternal syphilis prevalence in Malawi shows an increasing upward trend, with an estimated six times relative increase between 2014 and 2022 (0.28% to 1.73%) and strong associations with higher district-level HIV prevalence. Controlling syphilis depends on reaching vulnerable populations at the sub-national level, which may be disproportionately affected. Our findings support the move to integrate the elimination of mother-to-child transmission (EMTCT) of syphilis programs with existing prevention of mother-to-child transmission (PMTCT) of HIV programs.

The welfare effects of time reallocation: evidence from Daylight Saving Time

AbstractDaylight Saving Time (DST) is a widely adopted practice implemented by over 70 countries to align sunlight with day‐to‐day activities and reduce energy demands. However, we do not have a clear knowledge of how it affects individuals' welfare. Using a regression discontinuity combined with a difference‐in‐differences design, we find that the Spring DST transition causes a significant decline in life satisfaction. By inducing a reallocation of time, the transition into DST deteriorates sleep quality and increases time stress, which in turn affects physical and emotional health. Using an event study approach, we find that such effects persist for about six days after the DST transition. Conversely, we provide evidence that the Autumn DST transition gives rise to a significant increase in life satisfaction. Finally, using a simple cost‐benefit analysis, we discuss the potential benefits of ending DST.

CsMYB73 negatively regulates theanine accumulation mediated by CsGGT2 and CsGGT4 in tea shoots (Camellia sinensis).

Theanine metabolism is a necessary biological process during the planting and production of tea that determines tea quality. There is currently little knowledge about the transcriptional regulation of theanine metabolism in tea plants. In this study, we demonstrated that γ-glutamyl-transpeptidase CsGGT4, as a homologous protein of the theanine hydrolase CsGGT2, exhibited a higher theanine synthesis catalytic efficiency. Homology modeling and molecular docking showed that differential protein structures between CsGGT2 and CsGGT4 implied their different biological functions in tea plants. Theanine content correlated significantly with the expression of CsGGT2, CsGGT4 and the transcription factor CsMYB73 in tea shoots from different seasons. Additionally, CsMYB73 was confirmed to act as a nucleus-localized transcription factor (TF), directly interacts with the CsGGT2 and CsGGT4 promoters, serving as an activator of CsGGT2 and a suppressor of CsGGT4. Consequently, this leads to a negative association with theanine accumulation in tea shoots. Furthermore, the continuous increase in CsMYB73 produced a significantly increase in CsGGT2 expression and inhibited CsGGT4 expression. The present study reveals that the degradation of theanine has been observed to increase, concomitantly with the inhibition of theanine synthesis, resulting in a significant decline in the accumulation of theanine in tea shoots during the process of seasonal greening in 'Huangkui' leaves. This study contributes to the broader comprehension of the intricate transcriptional regulatory hierarchy that governs the metabolism of theanine in tea shoots, offering novel approaches for managing tea plantations and enhancing tea quality.

Plasma proenkephalin A and incident chronic kidney disease and albuminuria in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort

BackgroundPlasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.S.MethodsIn a nested cohort of 4,400 participants among the REasons for Geographic And Racial Differences in Stroke, we determined the association between baseline PENK-A concentration and incident CKD using the creatinine-cystatin C CKD-EPI 2021 equation without race coefficient, significant eGFR decline, and incident albuminuria between baseline and a follow-up visit 9.4 years later. We tested for race and sex interactions. We used inverse probability sampling weights to account for the sampling design.ResultsAt baseline, mean (SD) age was 64 (8) years, 49% were women, and 52% were Black participants. 8.5% developed CKD, 21% experienced ≥ 30% decline in eGFR and 18% developed albuminuria. There was no association between PENK-A and incident CKD and no difference by race or sex. However, higher PENK-A was associated with increased odds of progressive eGFR decline (OR: 1.12; 95% CI 1.00, 1.25). Higher PENK-A concentration was strongly associated with incident albuminuria among patients without diabetes mellitus (OR:1.29; 95% CI 1.09, 1.53).ConclusionWhile PENK-A was not associated with incident CKD, its associations with progression of CKD and incident albuminuria, among patients without diabetes, suggest that it might be a useful tool in the evaluation of kidney disease among White and Black patients.

Üzleti kilátások értékelése Ukrajna autóiparában: nemzeti és regionális vonatkozások

The study examines development trends and business perspectives in the automotive industry of Ukraine and particularly in Transcarpathia. The trends of the labor market in Ukraine have been identified, the state of migration processes, the level of unemployment in the regions of Ukraine have been assessed. The results of a comparative analysis of the level of the minimum wage in Ukraine in terms of regions, categories and positions are presented. The standard salary of back-office workers and management in the automotive sector was studied. The evolution of the regulatory and legal provision of state regulation of the development of the automobile industry in Ukraine is traced. Radical changes in the state policy of the development of the automotive industry of Ukraine were revealed: from constant support of car manufacturers and stimulation of car production to bureaucratic barriers, obstacles and existing risks and threats. It is stated that since 2014, Russia's armed aggression against Ukraine has led to a significant decline in the car industry. The effectiveness of the activities of the largest automotive industry companies in Zakarpattia Oblast was studied for the period 2018-2022. The financial indicators chosen for analysis were the capital-to-asset ratio, return on assets (ROA), return on equity (ROE) and net profit margin (NPM). A conclusion was made about the positive trend of increasing the volume of activity and improving the financial stability and profitability of companies over the past 5 years. From the point of view of investors, the most attractive is Eurocar, which demonstrates positive dynamics of the indicator and has the highest value of ROE among the selected companies at the end of 2022, namely 19.6%. Proximity to the border with the EU, cheap labor and sufficient raw materials make the western oblasts of Ukraine especially attractive for partnership with European auto giants. The need to create an automobile cluster in the region was emphasized.