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Paleontology provides insights into the history of the planet, from the origins of life billions of years ago to the biotic changes of the Recent. The scope of paleontological research is as vast as it is varied, and the field is constantly evolving. In an effort to identify “Big Questions” in paleontology, experts from around the world came together to build a list of priority questions the field can address in the years ahead. The 89 questions presented herein (grouped within 11 themes) represent contributions from nearly 200 international scientists. These questions touch on common themes including biodiversity drivers and patterns, integrating data types across spatiotemporal scales, applying paleontological data to contemporary biodiversity and climate issues, and effectively utilizing innovative methods and technology for new paleontological insights. In addition to these theoretical questions, discussions touch upon structural concerns within the field, advocating for an increased valuation of specimen-based research, protection of natural heritage sites, and the importance of collections infrastructure, along with a stronger emphasis on human diversity, equity, and inclusion. These questions offer a starting point—an initial nucleus of consensus that paleontologists can expand on—for engaging in discussions, securing funding, advocating for museums, and fostering continued growth in shared research directions.
Little is known regarding the shared genetic architecture underlying the phenotypic associations between depression and preterm birth (PTB). We aim to investigate the genetic overlap and causality of depression with PTB.
Methods
Leveraging summary statistics from the largest genome-wide association studies for broad depression (Ntotal = 807,533), major depression (Ntotal = 173,005), bipolar disorder (Ntotal = 414,466), and PTB (Ntotal = 226,330), we conducted a large-scale genome-wide cross-trait analysis to assess global and local genetic correlations, identify pleiotropic loci, and infer potential causal relationships
Results
Positive genetic correlations were observed between PTB and broad depression (rg = 0.242), major depression (rg = 0.236), and bipolar disorder (rg = 0.133) using the linkage disequilibrium score regression, which were further verified by the genetic covariance analyzer. Local genetic correlation was identified at chromosome 11q22.3 (harbors NCAM1-TTC12-ANKK1-DRD2) for PTB with depression. Cross-trait meta-analysis identified two loci shared between PTB and broad depression, two loci shared with major depression, and five loci shared with bipolar disorder, among which three were novel (rs7813444, rs3132948 and rs9273363). Mendelian randomization demonstrated a significantly increased risk of PTB for genetic liability to broad depression (odds ratio [OR]=1.30; 95% confidence interval [CI]: 1.11-1.52) and major depression (OR=1.27; 95%CI: 1.08-1.49), and the estimates remained significant across the sensitivity analyses.
Conclusions
Our findings demonstrate an intrinsic link underlying depression and PTB and shed novel light on the biological mechanisms, highlighting an important role of early screening and effective intervention of depression in PTB prevention, and may provide novel treatment strategies for both diseases.
Danon disease is an X-linked disorder caused by variants in the lysosome-associated membrane protein-2 (LAMP2) gene located on Xq24. Due to its inheritance in an X-chromosome dominant manner, males typically experience more severe manifestations than females.
Method:
The whole exome sequencing was conducted on a cohort of 218 children diagnosed with hypertrophic cardiomyopathy; four children with hypertrophic cardiomyopathy carrying the LAMP2 variants were diagnosed at our centre. Variants in the LAMP2 gene were summarised, and their pathogenicity and conservation were analysed using bioinformatics methods. A retrospective analysis of genotype-phenotype associations was also conducted in conjunction with previously reported cases.
Results:
Four patients with Danon disease were diagnosed in our single centre by gene sequencing; they all presented with myocardial hypertrophy as the initial manifestation. Both male patients manifested symptoms from infancy, while disease onset in the two female cases occurred below the average age reported for females. Through gene sequencing, a total of four variants were identified in these four patients, including one splicing variant: c.865-1G>C, one loss of heterozygosity variant: loss1 exon:4-9), one frameshift variant: c.973delG(p.(L325Wfs×21)), and one stop codon variant: c.467T>G(p.(L156*)).
Conclusion:
This study identified four patients with LAMP2 gene variants, thereby enriching the documented genetic landscape of LAMP2-associated disorders. Bioinformatics analyses corroborated the pathogenicity of these variants. Additionally, we emphasised that women with suspected Danon disease should be thoroughly evaluated, and the possibility of implantable cardioverter defibrillator implantation and heart transplantation should be considered and discussed as early as possible.
Social determinants of health (SDHs) exert a significant influence on various health outcomes and disparities. This study aimed to explore the associations between combined SDHs and mortality, as well as adverse health outcomes among adults with depression.
Methods
The research included 48,897 participants with depression from the UK Biobank and 7,771 from the US National Health and Nutrition Examination Survey (NHANES). By calculating combined SDH scores based on 14 SDHs in the UK Biobank and 9 in the US NHANES, participants were categorized into favourable, medium and unfavourable SDH groups through tertiles. Cox regression models were used to evaluate the impact of combined SDHs on mortality (all-cause, cardiovascular disease [CVD] and cancer) in both cohorts, as well as incidences of CVD, cancer and dementia in the UK Biobank.
Results
In the fully adjusted models, compared to the favourable SDH group, the hazard ratios for all-cause mortality were 1.81 (95% CI: 1.60–2.04) in the unfavourable SDH group in the UK Biobank cohort; 1.61 (95% CI: 1.31–1.98) in the medium SDH group and 2.19 (95% CI: 1.78–2.68) in the unfavourable SDH group in the US NHANES cohort. Moreover, higher levels of unfavourable SDHs were associated with increased mortality risk from CVD and cancer. Regarding disease incidence, they were significantly linked to higher incidences of CVD and dementia but not cancer in the UK Biobank.
Conclusions
Combined unfavourable SDHs were associated with elevated risks of mortality and adverse health outcomes among adults with depression, which suggested that assessing the combined impact of SDHs could serve as a key strategy in preventing and managing depression, ultimately helping to reduce the burden of disease.
To fully understand resilience and to inform resilience-promoting interventions, it is important to explore how resilience develops and the factors that influence it. Using a multidimensional approach that considers both well-being resilience (higher than expected wellbeing after adversity) and depression resilience (lower than expected depression after adversity), this study examined resilience trajectories among Chinese 0adolescents and the associations of gratitude and perceived stress with resilience trajectories. Data from a four-wave longitudinal study were analyzed from 563 Chinese adolescents (mean age at Time 1 = 12.83 years, 51.87% boys). Parallel-process latent class growth modeling identified four distinct trajectories of resilience development: flourishing resilience (increasing resilience; 21.67%), increasing wellbeing resilience but decreasing depression resilience (28.24%), declining resilience (29.48%), and increasing depression resilience but decreasing wellbeing resilience (20.61%). Gratitude was associated with greater odds of being in the flourishing resilience group. Furthermore, perceived stress was associated with lower odds of being in the flourishing resilience group and higher odds of being in the declining resilience group. The findings suggest that resilience is a dynamic and multidimensional construct with highly heterogeneous developmental trajectories. Gratitude and perceived stress may be effective targets for interventions to enhance adolescent resilience.
The incorporation of trace metals into land snail shells may record the ambient environmental conditions, yet this potential remains largely unexplored. In this study, we analyzed modern snail shells (Cathaica sp.) collected from 16 sites across the Chinese Loess Plateau to investigate their trace metal compositions. Our results show that both the Sr/Ca and Ba/Ca ratios exhibit minimal intra-shell variability and small inter-shell variability at individual sites. A significant positive correlation is observed between the shell Sr/Ca and Ba/Ca ratios across the plateau, with higher values being recorded in the northwestern sites where less monsoonal rainfall is received. We propose that shell Sr/Ca and Ba/Ca ratios, which record the composition of soil solution, may be controlled by the Rayleigh distillation in response to prior calcite precipitation. Higher rainfall amounts may lead to a lower degree of Rayleigh distillation and thus lower shell Sr/Ca and Ba/Ca ratios. This is supported by the distinct negative correlation between summer precipitation and shell Sr/Ca and Ba/Ca ratios, enabling us to reconstruct summer precipitation amounts using the Sr/Ca and Ba/Ca ratios of Cathaica sp. shells. The potential application of these novel proxies may also be promising for other terrestrial mollusks living in the loess deposits globally.
The whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is economically one of the most threatening pests in tomato cultivation, which not only causes direct damage but also transmits many viruses. Breeding whitefly-resistant tomato varieties is a promising and environmentally friendly method to control whitefly populations in the field. Accumulating evidence from tomato and other model systems demonstrates that flavonoids contribute to plant resistance to herbivorous insects. Previously, we found that high flavonoid-producing tomato line deterred whitefly oviposition and settling behaviours, and was more resistant to whiteflies compared to the near-isogenic low flavonoid-producing tomato line. The objective of the current work is to describe in detail different aspects of the interaction between the whitefly and two tomato lines, including biochemical processes involved. Electrical penetration graph recordings showed that high flavonoid-producing tomato reduced whitefly probing and phloem-feeding efficiency. We also studied constitutive and induced plant defence responses and found that whitefly induced stronger reactive oxygen species accumulation through NADPH oxidase in high flavonoid-producing tomato than in low flavonoid-producing tomato. Moreover, whitefly feeding induced the expression of callose synthase genes and resulted in callose deposition in the sieve elements in high flavonoid-producing tomato but not in low flavonoid-producing tomato. As a consequence, whitefly feeding on high flavonoid-producing tomato significantly decreased uptake of phloem and reduced its performance when compared to low flavonoid-producing tomato. These results indicate that high flavonoid-producing tomato provides phloem-based resistance against whitefly infestation and that the breeding of such resistance in new varieties could enhance whitefly management.
Previous studies have suggested that nature contact is a protective factor for problem behavior in children. However, there remains a significant gap in research exploring the reciprocal relationship between nature contact and children’s problem behavior, as well as the underlying mechanisms driving this relationship. This study employed a longitudinal three-wave design involving 516 children in China (268 girls, Mage = 10.88 ± 0.66 years old at Time 3). Cross-lagged analyses indicated that nature contact and problem behavior negatively predicted each other over time, and prosocial behavior bidirectionally mediated the relationship between nature contact and problem behavior. These results provided evidence for the relationships among nature interaction, social development, and behavioral development in children. These findings suggested that promoting prosocial behavior could reduce problem behavior and enhance nature engagement, potentially serving as a strategy to foster comprehensive development in children.
Recent studies have increasingly utilized gradient metrics to investigate the spatial transitions of brain organization, enabling the conversion of macroscale brain features into low-dimensional manifold representations. However, it remains unclear whether alterations exist in the cortical morphometric similarity (MS) network gradient in patients with schizophrenia (SCZ). This study aims to examine potential differences in the principal MS gradient between individuals with SCZ and healthy controls and to explore how these differences relate to transcriptional profiles and clinical phenomenology.
Methods
MS network was constructed in this study, and its gradient of the network was computed in 203 patients with SCZ and 201 healthy controls, who shared the same demographics in terms of age and gender. To examine irregularities in the MS network gradient, between-group comparisons were carried out, and partial least squares regression analysis was used to study the relationships between the MS network gradient-based variations in SCZ, and gene expression patterns and clinical phenotype.
Results
In contrast to healthy controls, the principal MS gradient of patients with SCZ was primarily significantly lower in sensorimotor areas, and higher in more areas. In addition, the aberrant gradient pattern was spatially linked with the genes enriched for neurobiologically significant pathways and preferential expression in various brain regions and cortical layers. Furthermore, there were strong positive connections between the principal MS gradient and the symptomatologic score in SCZ.
Conclusions
These findings showed changes in the principal MS network gradient in SCZ and offered potential molecular explanations for the structural changes underpinning SCZ.
This study examined global trends in influenza-associated lower respiratory infections (LRIs) deaths from 1990 to 2019 using data from the GBD 2019. The annual percentage change (APC) and average annual percentage change (AAPC) were used to analyze age-standardized death rates (ASDR). Globally, the ASDR of influenza-associated LRIs was 3.29/100,000 in 2019, which was higher in the African region (6.57/100,000) and among adults aged 70 years and older (29.88/100,000). The ASDR of influenza-associated LRIs decreased significantly from 1990 to 2019 (AAPC = −1.88%, P < 0.05). However, it was significantly increased among adults aged 70 years and older during 2017–2019 (APC = 2.31%, P < 0.05), especially in Western Pacific Region and South-East Asia Regions. The ratio of death rates between adults aged 70 years and older and children aged under 5 years increased globally from 1.63 in 1990 to 5.34 in 2019, and the Western Pacific Region experienced the most substantial increase, with the ratio soaring from 1.83 in 1990 to 12.98 in 2019. Despite a decline in the global ASDR of influenza-associated LRIs, it continues to impose a significant burden, particularly in the African, Western Pacific regions and among the elderly population.
Optical fibers offer convenient access to a variety of nonlinear phenomena. However, due to their inversion symmetry, second-order nonlinear effects, such as second-harmonic generation (SHG), are challenging to achieve. Here, all-fiber in-core SHG with high beam quality is achieved in a random fiber laser (RFL). The fundamental wave (FW) is generated in the same RFL. The phase-matching condition is mainly achieved through an induced periodic electric field and the gain is enhanced through the passive spatiotemporal gain modulation and the extended fiber. The conversion needs no pretreatment and the average second-harmonic (SH) power reaches up to 10.06 mW, with a corresponding conversion efficiency greater than 0.04%. Moreover, a theoretical model is constructed to explain the mechanism and simulate the evolution of the SH and FW. Our work offers a simple method to generate higher brightness for in-fiber SHs, and may further provide new directions for research on all-fiber χ(2)-based nonlinear fiber optics and RFLs.
Systematically monitoring the baseline sensitivity of troublesome weeds to herbicides is a crucial step in the early detection of their market lifespan. Florpyrauxifen-benzyl is one of the most important herbicides used in rice production throughout the world, and has been used for 5 yr in China. Barnyardgrass is one of the main targeted weed species of florpyrauxifen-benzyl. In total, 114 barnyardgrass populations were collected from rice fields in Jiangsu Province, China, and using whole-plant bioassays they were screened for susceptibility to florpyrauxifen-benzyl. The GR50 values (representing the dose that causes a 50% reduction in fresh weight of aboveground parts) of florpyrauxifen-benzyl for all populations ranged from 1.0 to 34.5 g ai ha−1, with an average of 6.8 g ai ha−1, a baseline sensitivity dose of 3.3 g ai ha−1, and a baseline sensitivity index of 34.5. Twenty-one days after treatment with florpyrauxifen-benzyl at the labeled dose (36 g ai ha−1), 90% of the barnyardgrass populations exhibited >95% reductions in fresh weight of aboveground parts. Compared with the baseline sensitivity dose, 63, 44, and 7 populations had, respectively, no resistance (55%), low resistance (39%), and moderate resistance (6%) to florpyrauxifen-benzyl. Furthermore, the GR50 distribution of barnyardgrass populations did not show a significant correlation with collection location, planting method (direct-seeding or transplanting), or rice species (Oryza sativa L. ssp. indica or ssp. japonica) at any of rice fields where seeds had been collected (P > 0.05). In conclusion, florpyrauxifen-benzyl remains effective for barnyardgrass control in rice fields despite serious resistance challenges.
Pemetrexed and immunotherapies (e.g., pembrolizumab) are approved for first-line maintenance (1LM) treatment of nonsquamous advanced/metastatic non-small-cell lung cancer (NSCLC), but real-world data on their use are limited. The objective of this study was to assess 1LM clinical outcomes, safety, and treatment patterns of immunotherapy versus immunotherapy+pemetrexed among patients with advanced/metastatic NSCLC from the EU4 (France, Germany, Italy, Spain)+UK.
Methods
Data from patients in the US, Canada, and EU4+UK with nonsquamous advanced/metastatic NSCLC without targetable mutations were collected via electronic case report form. Physician-identified patients (≥18 y) in the EU4+UK were eligible for this subgroup analysis if they achieved stable disease or complete or partial response with first-line platinum-based chemotherapy+immunotherapy (January 2019 to March 2021) and received 1LM immunotherapy or immunotherapy+pemetrexed. Patients were followed from index (1LM initiation) until last physician contact or death. Outcomes were overall survival (OS), progression-free survival (PFS), treatment patterns and duration, and adverse events.
Results
Among the selected 367 patients (male, 71.9%; mean±StDev age, 63.4±7.2 y; current/former smokers, 85.8%), 203 (55.3%) received immunotherapies, most commonly pembrolizumab (n=173; 85.2%), and 164 (44.7%) received immunotherapy+pemetrexed. Patients receiving immunotherapy had longer median adjusted OS and PFS compared to those receiving immunotherapy+pemetrexed (OS hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.36, 0.90; PFS HR: 0.58; 95% CI: 0.38, 0.79). Patients receiving immunotherapy versus patients receiving immunotherapy+pemetrexed had longer median treatment duration (14.0 vs 10.3 mo; p<0.001) and were less likely to experience anemia (19.7% vs 33.5%; p<0.01). Results were similar in the overall study population.
Conclusions
In this real-world study, among the selected patients with nonsquamous advanced/metastatic NSCLC who achieved stable disease or complete or partial response with first-line therapy, the addition of pemetrexed to immunotherapy in 1LM did not appear to confer a clinical benefit. Identifying treatments that can improve clinical outcomes for these patients remains an area of unmet need.
Despite growing awareness of the mental health damage caused by air pollution, the epidemiologic evidence on impact of air pollutants on major mental disorders (MDs) remains limited. We aim to explore the impact of various air pollutants on the risk of major MD.
Methods
This prospective study analyzed data from 170 369 participants without depression, anxiety, bipolar disorder, and schizophrenia at baseline. The concentrations of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), particulate matter with aerodynamic diameter > 2.5 μm, and ≤ 10 μm (PM2.5–10), nitrogen dioxide (NO2), and nitric oxide (NO) were estimated using land-use regression models. The association between air pollutants and incident MD was investigated by Cox proportional hazard model.
Results
During a median follow-up of 10.6 years, 9 004 participants developed MD. Exposure to air pollution in the highest quartile significantly increased the risk of MD compared with the lowest quartile: PM2.5 (hazard ratio [HR]: 1.16, 95% CI: 1.09–1.23), NO2 (HR: 1.12, 95% CI: 1.05–1.19), and NO (HR: 1.10, 95% CI: 1.03–1.17). Subgroup analysis showed that participants with lower income were more likely to experience MD when exposed to air pollution. We also observed joint effects of socioeconomic status or genetic risk with air pollution on the MD risk. For instance, the HR of individuals with the highest genetic risk and highest quartiles of PM2.5 was 1.63 (95% CI: 1.46–1.81) compared to those with the lowest genetic risk and lowest quartiles of PM2.5.
Conclusions
Our findings highlight the importance of air pollution control in alleviating the burden of MD.
Investigations are conducted on the effect of wall proximity on the flow around a cylinder under an axial magnetic field, using the electrical potential probe technology to measure the velocity of liquid metal flow. The study focused on the impact of the inlet velocity of the fluid, the magnetic field and wall proximity on the characteristics of velocity fields, particularly on the vortex-shedding mode. Based on different magnitudes of the magnetic field and the distance from the cylinder to the duct wall, three types of vortex-shedding modes are identified, (I) shear layer oscillation state, (II) quasi-two-dimensional vortex-shedding states and (III) transition of the magnetohydrodynamic to hydrodynamic Kármán street. The transitions between these modes are analysed in detail. The experimental results show that the weak wall-proximity effect leads to the formation of the Kármán vortex street, while a reverse Kármán vortex street and secondary vortices emerge under a strong wall-proximity effect. It is noticed that the Kelvin–Helmholtz instability drives vortex shedding under regime I, leading to an increase in the Strouhal number (St) with stronger magnetic fields. Additionally, under a strong axial magnetic field, the wall-proximity effect (‘Shercliff layer effect’) promotes the instability of shear layers on both sides of the cylinder. These unique coupling effects are validated by variations in modal coefficients and energy proportions under different vortex-shedding regimes using the proper orthogonal decomposition method.
During the investigation of parasitic pathogens of Mytilus coruscus, infection of a Perkinsus-like protozoan parasite was detected by alternative Ray's Fluid Thioglycolate Medium (ARFTM). The diameter of hypnospores or prezoosporangia was 8–27 (15.6 ± 4.0, n = 111) μm. The prevalence of the Perkinsus-like species in M. coruscus was 25 and 12.5% using ARFTM and PCR, respectively. The ITS1-5.8S-ITS2 fragments amplified by PCR assay had 100% homology to that of P. beihaiensis, suggesting that the protozoan parasite was P. beihaisensis and M. coruscus was its new host in East China Sea (ECS). Histological analysis showed the presence of trophozoites of P. beihaiensis in gill, mantle and visceral mass, and the schizonts only found in visceral mass. Perkinsus beihaiensis infection led to inflammatory reaction of hemocyte and the destruction of digestive tubules in visceral mass, which had negative effect on health of the farmed M. coruscus and it deserves more attention.
In this paper, a high-order-mode (HOM) (TE330) cavity-fed 45° linear polarized 6×6 slot array antenna is proposed. The 45° linear polarization is achieved by introducing asymmetric cross slots on the HOM cavity, resulting in low profile and wide bandwidth. The antenna array was verified using standard printed circuit board technology. Measured results show that the impedance bandwidth ( $|S_{11}|\le$ −10 dB) is 13.9% (36.98–42.92 GHz), and the peak gain is 19.3 dBi with a 3-dB gain bandwidth of 13.6%. Attributed to its simple structure, low profile, and wide bandwidth, the presented antenna is a good candidate for 5G applications.
Revealing the impact of forest succession processes on changes in plant diversity is crucial for understanding the mechanisms that maintain plant diversity across various succession stages. While previous research has predominantly focused on the influence of environmental factors or management strategies on plant diversity within rubber plantation understories, there is a scarcity of studies examining the effects of forest succession processes on plant diversity. This study focuses on the plant diversity of the understory herbaceous layer within the rubber forest of the Yinggeling area, located in National Park of Hainan Tropical Rainforest. It employs a spatial analysis approach, rather than a temporal one, to examine the characteristics of the understory herbaceous community. The findings revealed that (1) The understory of Yinggeling rubber plantations harbors 175 plant species from 149 genera and 75 families, with Gramineae and Rubiaceae representing 46.45% of total species. And the dominant families are Rubiaceae, Gramineae, and Moraceae, with Ficus and Pteris being the dominant genera. (2) The dominant species vary with succession duration, with Tetrastigma pachyphyllum dominating in 0-year succession, Paspalum conjugatum in 3-year succession, and Microstegium fasciculatum in 7-year succession. (3) Diversity indices such as the Shannon–Wiener index, Simpson index, and Pielou index peak at 7 years of natural succession, while the species richness is highest at 3 years. (4) The similarity coefficient between understory herbaceous plant communities in rubber plantations undergoing 0 and 3 years of natural succession is highest 0.56, indicating a significant similarity, while similarity is lowest between 0 and 7 years of succession. This research shows that natural restoration helps increase species diversity in the understory herb layer of rubber forests. Succession leads to changes in the dominant families, genera, and species of the herbaceous layer. This change can be attributed to the intraspecific competition and ecological competition that occur during the succession process, leading to changes in biological and resource allocation.