bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired esophagogastric junction relaxation and lung transplantation outcomes
Authors: Latorre-Rodríguez Andrés R , Golla Madison , Arjuna Ashwini , Bremner Ross M , Mittal Sumeet K
Published: May 2024

The implications of impaired esophagogastric junction relaxation (i.e. esophagogastric junction outflow obstruction and achalasia) in lung transplants recipients (LTRs) are unclear. Thus, we examined the prevalence and clinical outcomes of LTRs with an abnormally elevated integrated relaxation pressure (IRP) on high-resolution manometry before lung transplantation (LTx). After IRB approval, we reviewed data on LTRs who underwent LTx between January 2019 and August 2022 with a preoperative median IRP >15 mmHg. Differences in overall survival and chronic lung allograft dysfunction (CLAD)–free survival between LTRs with a normalized median IRP after LTx (N-IRP) and those with persistently high IRP (PH-IRP) were assessed using Kaplan–Meier curves and the log-rank test. During the study period, 352 LTx procedures were performed; 44 (12.5%) LTRs had an elevated IRP before LTx, and 37 (84.1%) completed a postoperative manometry assessment (24 [70.6%] males; mean age, 65.2 ± 9.1 years). The median IRP before and after LTx was 18.7 ± 3.8 mmHg and 12 ± 5.6 mmHg, respectively (P < 0.001); the median IRP normalized after LTx in 24 (64.9%) patients. Two-year overall survival trended lower in the N-IRP group than the PH-IRP group (77.2% vs. 92.3%, P = 0.086), but CLAD-free survival (P = 0.592) and rates of primary graft dysfunction (P = 0.502) and acute cellular rejection (P = 0.408) were similar. An abnormally elevated IRP was common in LTx candidates; however, it normalized in roughly two-thirds of patients after LTx. Two-year survival trended higher in the PH-IRP group, despite similar rates of primary graft dysfunction and acute cellular rejection as well as similar CLAD-free survival between the groups.
α-Synuclein pathology in Drosophila melanogaster is exacerbated by haploinsufficiency of Rop: connecting STXBP1 encephalopathy with α-synucleinopathies
Authors: Matsuoka Taro , Yoshida Hideki , Kasai Takashi , Tozawa Takenori , Iehara Tomoko , Chiyonobu Tomohiro
Published: May 2024

Syntaxin-binding protein 1 (STXBP1) is a presynaptic protein that plays important roles in synaptic vesicle docking and fusion. STXBP1 haploinsufficiency causes STXBP1 encephalopathy (STXBP1-E), which encompasses neurological disturbances including epilepsy, neurodevelopmental disorders, and movement disorders. Most patients with STXBP1-E present with regression and movement disorders in adulthood, highlighting the importance of a deeper understanding of the neurodegenerative aspects of STXBP1-E. An in vitro study proposed an interesting new role of STXBP1 as a molecular chaperone for α-Synuclein (αSyn), a key molecule in the pathogenesis of neurodegenerative disorders. However, no studies have shown αSyn pathology in model organisms or patients with STXBP1-E. In this study, we used Drosophila models to examine the effects of STXBP1 haploinsufficiency on αSyn-induced neurotoxicity in vivo. We demonstrated that haploinsufficiency of Ras opposite (Rop), the Drosophila ortholog of STXBP1, exacerbates compound eye degeneration, locomotor dysfunction, and dopaminergic neurodegeneration in αSyn-expressing flies. This phenotypic aggravation was associated with a significant increase in detergent-insoluble αSyn levels in the head. Furthermore, we tested whether trehalose, which has neuroprotective effects in various models of neurodegenerative disorders, mitigates αSyn-induced neurotoxicity exacerbated by Rop haploinsufficiency. In flies expressing αSyn and carrying a heterozygous Rop null variant, trehalose supplementation effectively alleviates neuronal phenotypes, accompanied by a decrease in detergent-insoluble αSyn in the head. In conclusion, this study revealed that Rop haploinsufficiency exacerbates αSyn-induced neurotoxicity by altering the αSyn aggregation propensity. This study not only contributes to understanding the mechanisms of neurodegeneration in STXBP1-E patients, but also provides new insights into the pathogenesis of α-synucleinopathies.
Depletion of protective microbiota promotes the incidence of fruit disease
Authors: Luo Xue , Sun Kai , Li Hao-Ran , Zhang Xiang-Yu , Pan Yi-Tong , Luo De-Lin , Wu Yi-Bo , Jiang Hui-Jun , Wu Xiao-Han , Ma Chen-Yu , Dai Chuan-Chao , Zhang Wei
Published: May 2024

Plant-associated microbiomes play important roles in plant health and productivity. However, despite fruits being directly linked to plant productivity, little is known about the microbiomes of fruits and their potential association with fruit health. Here, by integrating 16S rRNA gene, ITS high-throughput sequencing data, and microbiological culturable approaches, we reported that roots and fruits (pods) of peanut, a typical plant that bears fruits underground, recruit different bacterial and fungal communities independently of cropping conditions and that the incidence of pod disease under monocropping conditions is attributed to the depletion of Bacillus genus and enrichment of Aspergillus genus in geocarposphere. On this basis, we constructed a synthetic community (SynCom) consisting of three Bacillus strains from geocarposphere soil under rotation conditions with high culturable abundance. Comparative transcriptome, microbiome profiling, and plant phytohormone signaling analysis reveal that the SynCom exhibited more effective Aspergillus growth inhibition and pod disease control than individual strain, which was underpinned by a combination of molecular mechanisms related to fungal cell proliferation interference, mycotoxins biosynthesis impairment, and jasmonic acid–mediated plant immunity activation. Overall, our results reveal the filter effect of plant organs on the microbiome and that depletion of key protective microbial community promotes the fruit disease incidence.
Deazaflavin metabolite produced by endosymbiotic bacteria controls fungal host reproduction
Authors: Richter Ingrid , Hasan Mahmudul , Kramer Johannes W , Wein Philipp , Krabbe Jana , Wojtas K Philip , Stinear Timothy P , Pidot Sacha J , Kloss Florian , Hertweck Christian , Lackner Gerald
Published: May 2024

The endosymbiosis between the pathogenic fungus Rhizopus microsporus and the toxin-producing bacterium Mycetohabitans rhizoxinica represents a unique example of host control by an endosymbiont. Fungal sporulation strictly depends on the presence of endosymbionts as well as bacterially produced secondary metabolites. However, an influence of primary metabolites on host control remained unexplored. Recently, we discovered that M. rhizoxinica produces FO and 3PG-F420, a derivative of the specialized redox cofactor F420. Whether FO/3PG-F420 plays a role in the symbiosis has yet to be investigated. Here, we report that FO, the precursor of 3PG-F420, is essential to the establishment of a stable symbiosis. Bioinformatic analysis revealed that the genetic inventory to produce cofactor 3PG-F420 is conserved in the genomes of eight endofungal Mycetohabitans strains. By developing a CRISPR/Cas-assisted base editing strategy for M. rhizoxinica, we generated mutant strains deficient in 3PG-F420 (M. rhizoxinica ΔcofC) and in both FO and 3PG-F420 (M. rhizoxinica ΔfbiC). Co-culture experiments demonstrated that the sporulating phenotype of apo-symbiotic R. microsporus is maintained upon reinfection with wild-type M. rhizoxinica or M. rhizoxinica ΔcofC. In contrast, R. microsporus is unable to sporulate when co-cultivated with M. rhizoxinica ΔfbiC, even though the fungus was observed by super-resolution fluorescence microscopy to be successfully colonized. Genetic and chemical complementation of the FO deficiency of M. rhizoxinica ΔfbiC led to restoration of fungal sporulation, signifying that FO is indispensable for establishing a functional symbiosis. Even though FO is known for its light-harvesting properties, our data illustrate an important role of FO in inter-kingdom communication.
Biology and life table parameters of Paralobesia viteana (Lepidoptera: Tortricidae), grown on different grape cultivars
Authors: Laiton-Jimenez Laura , Samiksha Fnu , Acevedo Flor Edith
Published: May 2024

The grape berry moth, Paralobesia viteana (Clemens), is an important pest of cultivated grapes in eastern North America. Damage is caused directly by larval feeding of grape clusters and indirectly by increasing fruit susceptibility to fungal and bacterial pathogens. Despite the impact of grape berry moth on grapes being widely recognized, there is a lack of understanding of the influence that different grape cultivars may have on grape berry moth development, reproduction, and population dynamics. In this study, we constructed age–stage 2-sex life tables for grape berry moth fed on 5 grape cultivars: Concord, Niagara, Riesling, Chambourcin, and Vidal, to examine the effects of diet on insect population development, survival, reproduction, and demographic parameters such as net reproductive rate, intrinsic rate of increase, finite rate of increase, and mean generation time. Our findings reveal that grape cultivar significantly influenced the neonate wandering period, larval developmental time, adult and female longevity, pupal weight, adult preoviposition period, oviposition period, mean generation time, age–stage-specific life expectancy, and reproductive value of P. viteana. However, diet type did not affect grape berry moth total fecundity or other demographic parameters. The highest female reproductive value was observed at 30–40 days of age, indicating that control tactics implemented during this time frame would have the greatest impact on reducing population increase. This study provides critical information on the effects of different grape cultivars on grape berry moth development, reproduction, and demography. These insights could lead to the development of management strategies that improve pest control and reduce economic losses in vineyards.
Fate of synthetic chemicals in the agronomic insect pest Spodoptera littoralis: experimental feeding-contact assay and toxicokinetic model
Authors: Römer Clara I , Ashauer Roman , Escher Beate I , Höfer Kristin , Muehlebach Michel , Sadeghi-Tehran Pouria , Sherborne Neil , Buchholz Anke
Published: May 2024

Insecticides prevent or reduce insect crop damage, maintaining crop quality and quantity. Physiological traits, such as an insect’s feeding behavior, influence the way insecticides are absorbed and processed in the body (toxicokinetics), which can be exploited to improve species selectivity. To fully understand the uptake of insecticides, it is essential to study their total uptake and toxicokinetics independent of their toxic effects on insects. We studied the toxicokinetics (TK) of insecticidally inactive test compounds incorporating agro-like structural motifs in larvae of the Egyptian cotton leafworm (Spodoptera littoralis, Lepidoptera), and their distribution across all biological matrices, using laboratory experiments and modeling. We measured Spodoptera larval behavior and temporal changes of whole-body concentrations of test compounds during feeding on treated soybean leaf disks and throughout a subsequent depuration period. Differences in the distribution of the total quantities of compounds were found between the biological matrices leaf, larva, and feces. Rate constants for uptake and elimination of test compounds were derived by calibrating a toxicokinetic model to the whole-body concentrations. Uptake and elimination rate constants depended on the physicochemical properties of the test compounds. Increasing hydrophobicity increased the bioaccumulation potential of test compounds. Incomplete quantities in larval matrices indicated that some compounds may undergo biotransformation. As fecal excretion was a major elimination pathway, the variable time of release and number of feces pellets led to a high variability in the body burden. We provide quantitative models to predict the toxicokinetics and bioaccumulation potential of inactive insecticide analogs (parent compounds) in Spodoptera.
Prediagnostic plasma proteomics profile for hepatocellular carcinoma
Authors: Zhang Xinyuan , Zhao Longgang , Ngo Long H , Dillon Simon T , Gu Xuesong , Lai Michelle , Simon Tracey G , Chan Andrew T , Giovannucci Edward L , Libermann Towia A , Zhang Xuehong
Published: May 2024

Objective

Proteomics may discover pathophysiological changes related to hepatocellular carcinoma, an aggressive and lethal type of cancer with low sensitivity for early stage diagnosis.

Design

We measured 1305 prediagnostic (median = 12.7 years) SomaScan proteins from 54 pairs of healthy individuals who subsequently developed hepatocellular carcinoma and matched non–hepatocellular carcinoma control individuals from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Candidate proteins were validated in the independent, prospective UK Biobank Pharma Proteomics Project (UKB-PPP).

Results

In NHS and HPFS, we identified 56 elevated proteins in hepatocellular carcinoma with an absolute fold change of more than 1.2 and a Wald test P value less than .05 in conditional logistic regression analysis. Ingenuity pathway analysis identified enrichment of pathways associated with cell viability, adhesion, proteolysis, apoptosis, and inflammatory response. Four proteins—chitinase-3-like protein 1, growth differentiation factor 15, interleukin-1 receptor antagonist protein, and E-selectin—showed strong positive associations with hepatocellular carcinoma and were thus validated by enzyme-linked immunosorbent assay (odds ratio = 2.48-14.7, all P < .05) in the NHS and HPFS and by Olink platform (hazard ratio = 1.90-3.93, all P < .05) in the UKB-PPP. Adding these 4 proteins to a logistic regression model of traditional hepatocellular carcinoma risk factors increased the area under the curve from 0.67 to 0.87 in the NHS and HPFS. Consistently, model area under the curve was 0.88 for hepatocellular carcinoma risk prediction in the UKB-PPP.

Conclusion

However, the limited number of hepatocellular carcinoma patients in the cohorts necessitates caution in interpreting our findings, emphasizing the need for further validation in high-risk populations.
More than meets the eye: knowns and unknowns of the trafficking of small secreted proteins in Arabidopsis
Authors: Pečenková Tamara , Potocký Martin , Stegmann Martin
Published: May 2024

Small proteins represent a significant portion of the cargo transported through plant secretory pathways, playing crucial roles in developmental processes, fertilization, and responses to environmental stresses. Despite the importance of small secreted proteins, substantial knowledge gaps persist regarding the regulatory mechanisms governing their trafficking along the secretory pathway, and their ultimate localization or destination. To address these gaps, we conducted a comprehensive literature review, focusing particularly on trafficking and localization of Arabidopsis small secreted proteins with potential biochemical and/or signaling roles in the extracellular space, typically those within the size range of 101–200 amino acids. Our investigation reveals that while at least six members of the 21 mentioned families have a confirmed extracellular localization, eight exhibit intracellular localization, including cytoplasmic, nuclear, and chloroplastic locations, despite the presence of N-terminal signal peptides. Further investigation into the trafficking and secretion mechanisms of small protein cargo could not only deepen our understanding of plant cell biology and physiology but also provide a foundation for genetic manipulation strategies leading to more efficient plant cultivation.
gausSN: Bayesian time-delay estimation for strongly lensed supernovae
Authors: Hayes Erin E , Thorp Stephen , Mandel Kaisey S , Arendse Nikki , Grayling Matthew , Dhawan Suhail
Published: May 2024

We present gausSN, a Bayesian semiparametric Gaussian Process (GP) model for time-delay estimation with resolved systems of gravitationally lensed supernovae (glSNe). gausSN models the underlying light curve non-parametrically using a GP. Without assuming a template light curve for each SN type, gausSN fits for the time delays of all images using data in any number of wavelength filters simultaneously. We also introduce a novel time-varying magnification model to capture the effects of microlensing alongside time-delay estimation. In this analysis, we model the time-varying relative magnification as a sigmoid function, as well as a constant for comparison to existing time-delay estimation approaches. We demonstrate that gausSN provides robust time-delay estimates for simulations of glSNe from the Nancy Grace Roman Space Telescope and the Vera C. Rubin Observatory’s Legacy Survey of Space and Time (Rubin-LSST). We find that up to 43.6 per cent of time-delay estimates from Roman and 52.9 per cent from Rubin-LSST have fractional errors of less than 5  per cent. We then apply gausSN to SN Refsdal and find the time delay for the fifth image is consistent with the original analysis, regardless of microlensing treatment. Therefore, gausSN maintains the level of precision and accuracy achieved by existing time-delay extraction methods with fewer assumptions about the underlying shape of the light curve than template-based approaches, while incorporating microlensing into the statistical error budget. gausSN is scalable for time-delay cosmography analyses given current projections of glSNe discovery rates from Rubin-LSST and Roman.
The host dark matter haloes of the first quasars
Authors: Costa Tiago
Published: May 2024

If z > 6 quasars reside in rare, massive haloes, ΛCDM cosmology predicts they should be surrounded by an anomalously high number of bright companion galaxies. Here, I show that these companion galaxies should also move unusually fast. Using a new suite of cosmological, ‘zoom-in’ hydrodynamic simulations, I present predictions for the velocity distribution of quasar companion galaxies and its variation with quasar host halo mass at $z \, = \, 6$. Satellites accelerate as they approach the quasar host galaxy, producing a line-of-sight velocity profile that broadens with decreasing distance to the quasar host galaxy. This increase in velocity dispersion is particularly pronounced if the host halo mass is $\gtrsim 5 \times 10^{12} \, \rm M_\odot$. Typical line-of-sight speeds rise to $\approx 500 \, \rm km \, s^{-1}$ at projected radii $\sim 10 \, \rm kpc$. For about 10 per cent of satellites, they should exceed $800 \, \rm km \, s^{-1}$, with $\approx 5~{{\ \rm per\ cent}}$ of companions reaching line-of-sight speeds $\sim 1000 \, \rm km \, s^{-1}$. For lower host halo masses $\approx 5 \times 10^{11}{-}10^{12} \, \rm M_\odot$, the velocity profile of companion galaxies is significantly flatter. In this case, typical line-of-sight velocities are $\approx 250 \, \rm km \, s^{-1}$ and do not exceed $\approx 500 \, \rm km \, s^{-1}$. A comparison with existing Atacama Large Millimeter/submillimeter Array (ALMA), JWST and Multi-Unit Spectroscopic Explorer (MUSE) line-of-sight velocity measurements reveals that observed z > 6 quasar companions closely follow the velocity distribution expected for a host halo with mass $\gtrsim 5 \times 10^{12} \, \rm M_\odot$, ruling out a light host halo. Finally, through an estimate of ultraviolet and [$\rm O \, {\small III}$] luminosity functions, I show that the velocity distribution more reliably discriminates between halo mass than companion number counts, which are strongly affected by cosmic variance.
China, global economic disintegration, and the climate change challenge
Authors: Garnaut Ross
Published: May 2024

China has a large national interest in the success of the international effort to hold human-induced increases in temperature to 1.5 degrees above pre-industrial levels—and therefore in global net emissions falling to net zero by 2050. China is essential to the success of the global effort—as a supplier of competitively priced equipment for the zero-emissions world economy and as the world’s largest current source of greenhouse gas emissions. Success is more likely for China and the world with international specialization in line with global comparative advantage in goods production for the zero-emissions economy. This requires open international trade, with China supplying equipment to and drawing zero emissions semi-processed goods from abroad. Contemporary tendencies in international political economy make that difficult but not impossible.
Platonism and intra-mathematical explanation
Authors: Baron Sam
Published: May 2024

I introduce an argument for Platonism based on intra-mathematical explanation: the explanation of one mathematical fact by another. The argument is important for two reasons. First, if the argument succeeds then it provides a basis for Platonism that does not proceed via standard indispensability considerations. Second, if the argument fails, it can only do so for one of the three reasons: either because there are no intra-mathematical explanations, or because not all explanations are backed by dependence relations, or because some form of noneism—the view according to which non-existent entities possess properties and stand in relations—is true. The argument thus forces a choice between nominalism without noneism, intra-mathematical explanation, and a backing conception of explanation. You can have any two, but not all three.
Relationship Among Falls, Fear of Falling, and Physical Activity Level in Patients on Hemodialysis
Authors: Shirai Nobuyuki , Usui Naoto , Abe Yoshifumi , Tamiya Hajime , Amari Takashi , Kojima Sho , Mikami Kenta , Nagashima Mizuki , Shinozaki Nobuhito , Shimano Yu , Saitoh Masakazu
Published: May 2024

Objective

Patients on hemodialysis are highly susceptible to falls and fractures. Amplified apprehension regarding the fear of falling (FOF) constitutes a risk factor that restricts physical activity and escalates the probability of falls among the elderly population. This study aimed to elucidate the association between falls and FOF and physical activity in patients on hemodialysis.

Methods

A prospective cohort study was conducted across 9 centers. FOF was assessed using the Falls Efficacy Scale-International (FES-I). Physical activity was assessed using the Japanese version of the International Physical Activity Questionnaire short form. Subsequently, falls were monitored over a duration of 1 year. Logistic regression analysis was performed to evaluate the relationship between falls and FOF and physical activity. In addition, in the receiver operating characteristic analysis, the cutoff value of FES-I that predicts falls was determined using the Youden Index. A restricted cubic spline curve was utilized to analyze the nonlinear association between falls and the FES-I.

Results

A total of 253 patients on hemodialysis (70.0 [59.0–77.0] years old; 105 female [41.5%]) were included in the analysis. During the 1-year observation period, 90 (35.6%) patients experienced accidental falls. The median FES-I score was 36.0 (24.0–47.0) points, and patients with higher FES-I scores had more falls. Following adjusted logistic regression analysis, FES-I exhibited an independent association with falls (OR = 1.04; 95% CI = 1.01–1.06), but physical activity was not. The area under the receiver operating characteristic curve was 0.70 (95% CI = 0.64–0.77), and the FES-I threshold value for distinguishing fallers from non-fallers was determined as 37.5 points (sensitivity 65.6%, specificity 35.0%). A nonlinear relationship between falls and FES-I was observed.

Conclusion

FOF was associated with the incidence of falls in patients on hemodialysis.

Impact

The evaluation and implementation of interventions targeting the FOF may mitigate the risk of falls.
Role of epigenetic regulatory mechanisms in age‐related bone homeostasis imbalance
Authors: Zhong Yunyu , Zhou Xueer , Pan Zijian , Zhang Jiankang , Pan Jian
Published: May 2024

Alterations to the human organism that are brought about by aging are comprehensive and detrimental. Of these, an imbalance in bone homeostasis is a major outward manifestation of aging. In older adults, the decreased osteogenic activity of bone marrow mesenchymal stem cells and the inhibition of bone marrow mesenchymal stem cell differentiation lead to decreased bone mass, increased risk of fracture, and impaired bone injury healing. In the past decades, numerous studies have reported the epigenetic alterations that occur during aging, such as decreased core histones, altered DNA methylation patterns, and abnormalities in noncoding RNAs, which ultimately lead to genomic abnormalities and affect the expression of downstream signaling osteoporosis treatment and promoter of fracture healing in older adults. The current review summarizes the impact of epigenetic regulation mechanisms on age‐related bone homeostasis imbalance.
Delayed presentation and management approach of autonomic dysfunction associated with severe tetanus
Authors: Hashi Abdullahi Said , Adam Abdirahim Ali Nur , Mohamed Isak
Published: May 2024

Introduction:

In 2019, there were over 73 000 estimated tetanus cases globally, including more than 27 000 cases of neonatal tetanus, and the worldwide deaths caused by tetanus were almost 34 684. The mortality rate of tetanus is greater than 50% in countries without ICUs and 10% in developed countries, mostly attributed to autonomic dysfunction. Countries with the greatest rates of post-neonatal tetanus mortality (greater than five fatalities per 100 000 people) were Somalia, South Sudan, and Kenya.

Case presentation:

A 66-year-old unvaccinated male patient came to our hospital emergency department with generalized rigidity, neck stiffness, lockjaw, and an altered level of consciousness for 5 days. His symptoms started with stiffness in his neck and back 4 days before. The patient was diagnosed with tetanus, as he was unimmunized, had a recent injury, and presented clinical findings. The authors started treatment by administering intramuscular human tetanus immunoglobulin and metronidazole. He was admitted to the ICU and placed in an isolation room with minimal auditory and visual stimuli. Following 2 weeks after admission his blood pressure began to fall, and his pulse rate started to fluctuate with alternating tachycardia and bradycardia. After 1 month in the ICU, he was discharged from the ICU and transferred to the ward. A catch-up immunization regimen was established.

Clinical discussion:

Tetanus is a rare condition in the Western world, primarily due to widespread vaccination programs from infancy to adulthood. There are crucial barriers that still exist to overcoming this disease in our country, including a lack of reliable immunization programs. In tetanus, the increase in survival is associated with the use of intensive care facilities for the management of tetanus, besides expanding the knowledge of the disease, which is a challenge for developing countries.

Conclusion:

It is essential to have enough immunization at an early stage of trauma since severe autonomic dysfunction linked to tetanus might be lethal.
Effect of hormone therapy on blood pressure and hypertension in postmenopausal women: a systematic review and meta-analysis
Authors: Ferreira Campos Luana , de Andrade Costa Guilherme , Domingues Feitosa Marina , Ferreira Félix Iuri , Gabrielli Ligia , C. Almeida Maria da Conceição , ML Aquino Estela , Aras Júnior Roque
Published: May 2024

Importance

Menopausal hormone therapy (HT) includes a wide variety of hormonal compounds, and its effect on blood pressure is still uncertain.

Objective

The aim of this study was to assess evidence regarding the effect of HT on blood pressure in postmenopausal women and its association with arterial hypertension.

Evidence Review

This systematic review and meta-analysis included randomized clinical trials and prospective observational studies. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of hypertension were assessed. All stages were independently performed by two reviewers. For blood pressure outcome, standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated as effect measures. Heterogeneity was assessed using the I
2 statistic. The results are presented based on the HT type. The incidence of hypertension was compared using descriptive analyses.

Findings

Eleven studies were included with 81,041 women evaluated, of which 29,812 used HT. The meta-analysis, conducted with 8 studies and 1,718 women, showed an increase in SBP with the use of oral conjugated equine estrogens plus progestogen (SMD = 0.60 mm Hg, 95% CI = 0.19 to 1.01). However, oral or transdermal use of estradiol plus progestogen (SMD = −2.00 mm Hg, 95% CI = −7.26 to 3.27), estradiol alone, and tibolone did not show any significant effect. No significant effect on DBP was observed for any formulation. Women who used oral estrogen plus progestogen had a higher risk of incident hypertension than those who never used it.

Conclusions and Relevance

The effect of HT on blood pressure is influenced by the formulation used, especially the type of estrogen. The combined formulations of conjugated equine estrogens plus progestogen increased SBP and the risk of hypertension, which was not observed among estradiol plus progestogen, estradiol alone, and tibolone users.
Association of muscle disorders in late postmenopausal women according to the type of experienced menopause
Authors: Vallejo María S. , Blümel Juan E. , Chedraui Peter , Tserotas Konstantinos , Salinas Carlos , Rodrigues Marcio A. , Rodríguez Doris A. , Rey Claudia , Ojeda Eliana , Ñañez Mónica , Monterrosa-Castro Álvaro , Gómez-Tabares Gustavo , Espinoza María T. , Escalante Carlos , Elizalde Alejandra , Dextre Maribel , Calle Andrés , Aedo Sócrates
Published: May 2024

Objective

Musculoskeletal disorders frequently affect postmenopausal women. This study aims to compare muscle disorders between women according to the type of experienced menopause: premature (PM) or normal age of menopause (NAM).

Methods

This was a cross-sectional study conducted in nine Latin American countries in which late postmenopausal women (55 to 70 years) were surveyed with a general questionnaire, the Menopause Rating Scale (MRS: item #4 exploring musculoskeletal discomfort), and strength, assistance with walking, rising from a chair, climbing stairs, and falling questionnaire (risk of sarcopenia).

Results

A total of 644 women were included: 468 who had NAM, and 176 who had PM (116 spontaneous and 60 surgical). The overall mean age of the participants was 60.9 ± 4.2 years. Women who had PM experienced more musculoskeletal discomfort (33.5% vs 20.9%, P < 0.001) and a higher likelihood of sarcopenia (35.2% vs 19.9%, P < 0.001) than women who had a NAM. Women who had surgical PM exhibited a higher prevalence of severe musculoskeletal discomfort (46.7% vs 29.3%, P < 0.02) and a higher likelihood of sarcopenia (45.0% vs 27.6%, P < 0.02) than women who had a NAM. After adjusting for covariates (age, body mass index, menopausal hormone therapy use, physical activity, education, cigarette consumption, use of antidepressants, sexual activity, comorbidities, and having a partner), our logistic regression model determined that spontaneous PM was not associated with higher odds of musculoskeletal discomfort and higher odds of sarcopenia. On the other hand, women who had surgical PM were more likely to experience musculoskeletal discomforts (odds ratio: 2.26; 95% confidence interval: 1.22-4.17) and higher odds for sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.16-3.65) as compared to women who experienced a NAM.

Conclusions

Women experiencing surgical PM have a higher likelihood of developing muscle disorders. This underscores the potential significance of hormonal levels in influencing musculoskeletal health during postmenopause.
Recommended measurement instruments for menopausal vasomotor symptoms: the COMMA (Core Outcomes in Menopause) consortium
Authors: Lensen Sarah , Paramanandam Vincent S. , Gabes Michaela , Kann Gesina , Donhauser Theresa , Waters Niamh F. , Li Anna D. , Peate Michelle , Susanto Nipuni S. , Caughey Lucy E. , Rangoonwal Fatema , Liu Jingbo , Condron Patrick , Anagnostis Panagiotis , Archer David F. , Avis Nancy E. , Bell Robin J. , Carpenter Janet S. , Chedraui Peter , Christmas Monica , Davies Melanie , Hillard Tim , Hunter Myra S. , Iliodromiti Stamatina , Jaff Nicole G. , Jaisamrarn Unnop , Joffe Hadine , Khandelwal Sunila , Kiesel Ludwig , Maki Pauline M. , Mishra Gita D. , Nappi Rossella E. , Panay Nick , Pines Amos , Roberts Helen , Rozenberg Serge , Rueda Camilo , Shifren Jan , Simon James A. , Simpson Paul , Siregar Muhammad Fidel Ganis , Stute Petra , Garcia Joan Tan , Vincent Amanda J. , Wolfman Wendy , Hickey Martha
Published: May 2024

Objective

The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects.

Methods

A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome.

Results

A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of “side effects” were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice.

Conclusions

We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.
Circulating metabolic biomarkers and risk of new-onset hypertension: findings from the UK Biobank
Authors: Zhou Yan-Feng , Ye Yi-Xiang , Chen Jun-Xiang , Zhang Yan-Bo , Wang Yi , Lu Qi , Geng Tingting , Liu Gang , Pan An
Published: May 2024

Objective:

The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension.

Methods:

We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs).

Results:

During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24–1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66–0.87) had the strongest association when comparing the highest to the lowest quintile. In general, very-low-density lipoprotein (VLDL) particles were positively, whereas high-density lipoprotein (HDL) particles were inversely associated with risk of hypertension. Similar patterns of cholesterol, phospholipids, and total lipids within VLDL and HDL particles were observed. Triglycerides within all lipoproteins were positively associated with hypertension risk. Other metabolites showed significant associations with risk of hypertension included amino acids, fatty acids, ketone bodies, fluid balance and inflammation markers. Adding 10 selected metabolic biomarkers to the traditional hypertension risk model modestly improved discrimination (C-statistic from 0.745 to 0.752, P < 0.001) for prediction of 10-year hypertension incidence.

Conclusion:

Among UK adults, disturbances in metabolic biomarkers are associated with incident hypertension. Comprehensive metabolomic profiling may provide potential novel biomarkers to identify high-risk individuals.
Validation of oscillometric ratio and maximum gradient methods for non-invasive blood pressure measurement with intra-arterial blood pressure measurements as reference
Authors: Celler Branko G. , Yong Andy , Rubenis Imants , Butlin Mark , Argha Ahmadreza , Rehan Rajan , Avolio Alberto
Published: May 2024

Most non-invasive blood pressure (BP) measurements are carried out using instruments which implement either the Ratio or the Maximum Gradient oscillometric method, mostly during cuff deflation, but more rarely during cuff inflation. Yet, there is little published literature on the relative advantages and accuracy of these two methods. In this study of 40 lightly sedated individuals aged 64.1 ± 9.6 years, we evaluate and compare the performance of the oscillometric ratio (K) and gradient (Grad) methods for the non-invasive estimation of mean pressure, SBP and DBP with reference to invasive intra-arterial values. There was no significant difference between intra-arterial estimates of mean pressure made via Korotkoff sounds (MP-OWE) or the gradient method (MP-Grad). However, 17.7% of MP-OWE and 15% of MP-Grad were in error by more than 10 mmHg. SBP-K and SBP-Grad underestimated SBP by 14 and 18 mmHg, whilst accurately estimating DBP with mean errors of 0.4 ± 5.0 and 1.7 ± 6.1 mmHg, respectively. Relative to the reference standard SBP-K, SBP-Grad and DBP-Grad were estimated with a mean error of -4.5 ± 6.6 and 1.4 ± 5.6 mmHg, respectively, noting that using the full range of recommended ratios introduces errors of 12 and 7 mmHg in SBP and DBP, respectively. We also show that it is possible to find ratios which minimize the root mean square error (RMSE) and the mean error for any particular individual cohort. We developed linear models for estimating SBP and SBP-K from a range of demographic and non-invasive OWE variables with resulting mean errors of 0.15 ± 5.6 and 0.3 ± 5.7 mmHg, acceptable according to the Universal standard.
The role of preterm birth in stress-induced sodium excretion in young adults
Authors: Tully Nicholas W. , Chappell Mark C. , Evans Joni K. , Jensen Elizabeth T. , Shaltout Hossam A. , Washburn Lisa K. , South Andrew M.
Published: May 2024

Background:

Early-life programming due to prematurity and very low birth weight (VLBW, <1500 g) is believed to contribute to development of hypertension, but the mechanisms remain unclear. Experimental data suggest that altered pressure natriuresis (increased renal perfusion pressure promoting sodium excretion) may be a contributing mechanism. We hypothesize that young adults born preterm will have a blunted pressure natriuresis response to mental stress compared with those born term.

Methods:

In this prospective cohort study of 190 individuals aged 18–23 years, 156 born preterm with VLBW and 34 controls born term with birth weight at least 2500 g, we measured urine sodium/creatinine before and after a mental stress test and continuous blood pressure before and during the stress test. Participants were stratified into groups by the trajectory at which mean arterial pressure (MAP) increased following the test. The group with the lowest MAP trajectory was the reference group. We used generalized linear models to assess poststress urine sodium/creatinine relative to the change in MAP trajectory and assessed the difference between groups by preterm birth status.

Results:

Participants’ mean age was 19.8 years and 57% were women. Change in urine sodium/creatinine per unit increase in MAP when comparing middle trajectory group against the reference group was greater in those born preterm [β 5.4%, 95% confidence interval (95% CI) -11.4 to 5.3] than those born term (β 38.5%, 95% CI -0.04 to 92.0), interaction term P = 0.002.

Conclusion:

We observed that, as blood pressure increased following mental stress, young adults born preterm exhibited decreased sodium excretion relative to term-born individuals.
Multiple urinary peptides are associated with hypertension: a link to molecular pathophysiology
Authors: Mavrogeorgis Emmanouil , Kondyli Margarita , Mischak Harald , Vlahou Antonia , Siwy Justyna , Rossing Peter , Campbell Archie , Mels Carina M.C. , Delles Christian , Staessen Jan A. , Latosinska Agnieszka , Persu Alexandre
Published: May 2024

Objectives:

Hypertension is a common condition worldwide; however, its underlying mechanisms remain largely unknown. This study aimed to identify urinary peptides associated with hypertension to further explore the relevant molecular pathophysiology.

Methods:

Peptidome data from 2876 individuals without end-organ damage were retrieved from the Human Urinary Proteome Database, belonging to general population (discovery) or type 2 diabetic (validation) cohorts. Participants were divided based on systolic blood pressure (SBP) and diastolic BP (DBP) into hypertensive (SBP ≥140 mmHg and/or DBP ≥90 mmHg) and normotensive (SBP <120 mmHg and DBP <80 mmHg, without antihypertensive treatment) groups. Differences in peptide abundance between the two groups were confirmed using an external cohort (n = 420) of participants without end-organ damage, matched for age, BMI, eGFR, sex, and the presence of diabetes. Furthermore, the association of the peptides with BP as a continuous variable was investigated. The findings were compared with peptide biomarkers of chronic diseases and bioinformatic analyses were conducted to highlight the underlying molecular mechanisms.

Results:

Between hypertensive and normotensive individuals, 96 (mostly COL1A1 and COL3A1) peptides were found to be significantly different in both the discovery (adjusted) and validation (nominal significance) cohorts, with consistent regulation. Of these, 83 were consistently regulated in the matched cohort. A weak, yet significant, association between their abundance and standardized BP was also observed.

Conclusion:

Hypertension is associated with an altered urinary peptide profile with evident differential regulation of collagen-derived peptides. Peptides related to vascular calcification and sodium regulation were also affected. Whether these modifications reflect the pathophysiology of hypertension and/or early subclinical organ damage requires further investigation.
TNF-α inhibitor use during pregnancy and the risk of preeclampsia: population-based cohort study
Authors: Adomi Motohiko , McElrath Thomas F. , Hernández-Díaz Sonia , Vine Seanna M. , Huybrechts Krista F.
Published: May 2024

Background:

Although the clinical importance of preeclampsia is widely recognized, few treatment options are available for prevention. TNF-α inhibitors have been hypothesized to potentially prevent the disease. We aimed to examine whether exposure to TNF-α inhibitors during pregnancy reduces the risk of preeclampsia.

Methods:

We conducted a population-based pregnancy cohort study using nationwide samples of publicly (Medicaid data, 2000–2018) and commercially (MarketScan Research Database, 2003–2020) insured pregnant women linked to their liveborn infants. Exposure was ascertained based on a filled prescription or administration code for TNF-α inhibitors during the first and second trimester of pregnancy. The outcomes included early-onset preeclampsia, late-onset preeclampsia, and small-for-gestational age. For baseline confounding adjustment, we leveraged propensity score overlap weights to estimate risk ratios (RR).

Results:

Among 4 315 658 pregnancies in the Medicaid and the MarketScan cohort, 2736 (0.063%) were exposed to TNF-α inhibitors during the first trimester and 1712 (0.040%) during the second trimester. After adjustment, the risk of early-onset preeclampsia was not decreased among mothers exposed during the first trimester compared with unexposed women with treatment indications [RRpooled: 1.25, 95% confidence interval (CI) 0.93–1.67]. Similarly, the risk of late-onset preeclampsia was not decreased among mothers exposed during the second trimester compared with unexposed women (RRpooled: 0.99, 95% CI 0.81–1.22).

Conclusion:

Contrary to the hypothesis, exposure to TNF-α inhibitors during pregnancy did not appear to be associated with a reduced risk of early-onset or late-onset preeclampsia. These findings do not support consideration of the use of TNF-α inhibitors for the prevention of preeclampsia.
Asprosin contributes to vascular remodeling in hypertensive rats via superoxide signaling
Authors: Xu Zhi-Qin , Li Xiu-Zhen , Zhu Rong , Ge Rui , Wei Hui , Shi Hong-Wei , Wang Zhe , Yang Cuan , Yang Ya-Wen , Lu Xue-Juan , Chen Ai-Dong , Zhu Guo-Qing , Tan Xiao
Published: May 2024

Objective:

Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling. Asprosin, a newly discovered protein hormone, is involved in metabolic diseases. Little is known about the roles of asprosin in cardiovascular diseases. This study focused on the role and mechanism of asprosin on VSMC proliferation and migration, and vascular remodeling in a rat model of hypertension.

Methods and results:

VSMCs were obtained from the aortic media of 8-week-old male Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Asprosin was upregulated in the VSMCs of SHR. For in vitro studies, asprosin promoted VSMC proliferation and migration of WKY and SHR, and increased Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, NOX1/2/4 protein expressions and superoxide production. Knockdown of asprosin inhibited the proliferation, migration, NOX activity, NOX1/2 expressions and superoxide production in the VSMCs of SHR. The roles of asprosin in promoting VSMC proliferation and migration were not affected by hydrogen peroxide scavenger, but attenuated by superoxide scavenger, selective NOX1 or NOX2 inhibitor. Toll-like receptor 4 (TLR4) was upregulated in SHR, TLR4 knockdown inhibited asprosin overexpression-induced proliferation, migration and oxidative stress in VSMCs of WKY and SHR. Asprosin was upregulated in arteries of SHR, and knockdown of asprosin in vivo not only attenuated oxidative stress and vascular remodeling in aorta and mesentery artery, but also caused a subsequent persistent antihypertensive effect in SHR.

Conclusions:

Asprosin promotes VSMC proliferation and migration via NOX-mediated superoxide production. Inhibition of endogenous asprosin expression attenuates VSMC proliferation and migration, and vascular remodeling of SHR.