Browse Articles

Gallstones as a predictor of elevated cardiovascular disease risk: A meta-analysis and meta-regression of over 7.4 million participants

Introduction Gallstone disease (GD) is a prevalent condition frequently encountered in surgical units worldwide. The objective of this comprehensive systematic review and meta-analysis study was to examine the relationship between gallstones and the risk of cardiovascular diseases (CVDs). Methods To conduct our study, we performed a systematic review and meta-analysis. We gathered relevant studies from reputable databases, including Web of Science, Scopus, PubMed, Cochrane, Google Scholar, and Embase. The quality of the articles was assessed using the Newcastle-Ottawa Scale checklist. To assess heterogeneity among the studies, we utilized statistical tests such as the Chi-square test, I² statistic, and forest plots. Meta-regression analysis considered variables such as the year of the study, study design, sample size, study quality assessment score, geographical region, average age of subjects, and follow-up duration. Additionally, we evaluated publication bias using Begg’s and Egger’s tests. Results Data from 22 studies conducted between 1985 and 2023 were analyzed. The combined number of participants across these studies was 7,496,303. The meta-analysis results revealed that individuals with GD had a higher risk of CVDs (Risk Ratio (RR): 1.29; 95% CI: 1.22–1.36; P <  0.001). Subgroup analysis showed consistent results across good quality studies (RR: 1.20, 95% CI: 11.12–1.28; P <  0.001), moderate quality studies (RR: 1.41, 95% CI: 1.15–1.74; P <  0.001), and low-quality studies (RR: 1.22, 95% CI: 1.15–1.30; P <  0.001). In the meta-regression analysis, none of the variables had a significant relationship with the observed heterogeneity (P-value > 0.10). In a sensitivity analysis, the estimated RR remained consistent, confirming the robustness of the meta-analysis results. Conclusion Our findings suggest an association between gallstone disease and an increased risk of CVDs. It seems that one of the important factors of this relationship is having common causes for the formation of gallstones and cardiovascular diseases. However, gallstones can be considered an important sign of increased risk of cardiovascular diseases.

Poverty alleviation resettlement in China reduces deforestation

Deforestation frequently accompanies poverty, yet various antipoverty programs in many countries have exhibited mixed results in addressing deforestation. Poverty Alleviation Resettlement (PAR) stands out as one of the few government-led resettlement programs designed to alleviate poverty, offering comprehensive follow-up support for quality of life and employment after relocation. Our study uncovered empirical evidence of the PAR program’s impact on forest quality. Through a multiperiod difference-in-differences analysis of remote sensing and household survey data, we found that the PAR program significantly curbed deforestation in the participating counties and reduced forest-clearing activities among the resettled households, even those relocating to rural villages. Mechanism analysis revealed that the program discouraged deforestation by enhancing market accessibility, fostering nonfarm employment opportunities, and elevating income levels. The study underscores that altering livelihood strategies and lifestyles is essential for resettlement programs to effectively mitigate ecological degradation.

Climate’s firm grip on glacier ablation in the Cordillera Darwin Icefield, Tierra del Fuego

Abstract The Cordillera Darwin Icefield (CDI) in Tierra del Fuego is one of the largest temperate ice bodies in the Southern Hemisphere. We simulate the climatic energy and mass balance of its glaciers (2000–2023), which are sensitive indicators of climatic changes in the Southern Hemisphere’s higher mid-latitudes. Year-round westerly winds cause strong climatic gradients across the mountain range, reflected in the energy and mass fluxes. Our results reveal a significant increase in surface melt (+0.18 m w.e. yr-1 per decade) over the past two decades. We also present the first estimate of dynamically controlled mass loss into adjacent fjords and lakes by frontal ablation, amounting to 1.44 ± 0.94 Gt yr-1 (26 % of the total CDI mass loss). Frontal losses are mainly channelized through few marine-terminating glaciers. While frontal ablation is important for predicting the fate of individual glaciers, for the CDI as a whole, atmospheric conditions exert the main control on the current glacier evolution.

Relationship between Pb ion off-centering and lone pair electrons

Abstract High-pressure synthesized Pb-based perovskites exhibit diverse functional properties. PbCrO3, for instance, displays distinctive diffuse scattering and valence skipping, forming Pb2+ and Pb4+ ions. However, the spatial distribution of Pb ions in the crystal remains largely unexplored. Here, we elucidate the role of Pb ions with different valences through Sr substitution, using high-resolution transmission electron microscopy combined with elemental mapping. This approach allows us to accurately examine the distribution of Sr and Pb ions in the same atomic columns. The results reveal that in Pb0.8Sr0.2CrO3, Sr ions occupy a squared lattice, while Pb ions exhibit positional distortions. Simulations based on the experimentally determined Pb distribution reproduce the diffuse scattering observed in PbCrO3. These findings suggest that the lone pair electrons of s orbitals are responsible for the local lattice distortion. Our study provides atomistic insights into the local structures of materials exhibiting valence skipping.

Fluorescence detection of dopamine signaling to the primate striatum in relation to stimulus–reward associations

Dopamine (DA) signals to the striatum play critical roles in shaping and sustaining stimulus-reward associations. In primates, however, the dynamics of the DA signals remain unknown since conventional methods are not necessarily appropriate in terms of the spatiotemporal resolution or chemical specificity sufficient for detecting the DA signals. In our study, fiber photometry with a fluorescent DA sensor was employed to identify reward-related DA transients in the monkey striatum. This technique, which directly monitors local DA release, reveals a reward prediction error signal in the anterior putamen originating from midbrain DA neurons. Further, DA transients in the head of the caudate nucleus exhibit a value-based response to reward-predicting stimuli. These signals have been found to arise from two separate groups of DA neurons in the substantia nigra pars compacta. The present results demonstrate that fluorescence DA monitoring is applicable to detect DA signals in the primate striatum for investigating their roles.

Contributions of biological and physical dynamics to deglacial CO2 release from the polar Southern Ocean

Hard label adversarial attack with high query efficiency against NLP models

Spinal TRPC3 promotes neuropathic pain and coordinates phospholipase C–induced mechanical hypersensitivity

Neuropathic pain is a debilitating chronic condition mainly caused by peripheral nerve injury. However, the cellular and molecular mechanisms underlying this condition remain unclear. Transient receptor potential canonical 3 (TRPC3), a TRP channel that is activated by downstream of the Gq-phospholipase C (PLC) axis, is expressed in the somatosensory system. Therefore, the present study investigated its pathophysiological role in neuropathic pain following peripheral nerve injury. Here, partial sciatic nerve ligation (pSNL) elicited mechanical and thermal hypersensitivity in wild-type mice, which was suppressed in TRPC3-KO mice. In situ hybridization revealed that TRPC3 is predominantly expressed in neurons in the spinal dorsal horn. Furthermore, spinal dorsal horn neuron-specific downregulation using miRNA attenuated pSNL-induced mechanical hypersensitivity. Spinal TRPC3 activation elicited acute mechanical hypersensitivity. Moreover, its genetic ablation reduced the mechanical hypersensitivity caused by spinal NK 1 R or PLC activation. These findings demonstrate that TRPC3 in spinal dorsal horn neurons facilitates the development of neuropathic pain. Therefore, TRPC3 may be a promising therapeutic target for neuropathic pain caused by peripheral nerve injury.

Unraveling the neurophysiological correlates of phase-specific enhancement of motor memory consolidation via slow-wave closed-loop targeted memory reactivation

Abstract Memory consolidation can be enhanced during sleep using targeted memory reactivation (TMR) and closed-loop (CL) acoustic stimulation on the up-phase of slow oscillations (SOs). Here, we test whether applying TMR at specific phases of the SOs (up vs. down vs. no reactivation) can influence the behavioral and neural correlates of motor memory consolidation in healthy young adults. Results show that up- (as compared to down-) state cueing results in greater performance improvement. Sleep electrophysiological data indicate that up- (as compared to down-) stimulated SOs exhibits higher amplitude and greater peak-nested sigma power. Task-related functional magnetic resonance images reveal that up-state cueing strengthens activity in - and segregation of - striato-motor and hippocampal networks; and that these modulations are related to the beneficial effect of TMR on sleep features and performance. Overall, these findings highlight the potential of CL-TMR to induce phase-specific modulations of motor performance, sleep oscillations and brain responses during motor memory consolidation.

Validating a willingness to share measure of a vignette experiment using real-world behavioral data

Abstract Willingness measures are widely employed in vignette and conjoint experiments. However, the predictive validity of these measures relies on the degree to which expressed intentions correspond with behavior in the real world. This study uses a unique research design that enables to validate an intention measure. In a 2022 online survey, respondents expressed their willingness to donate their social media data in hypothetical scenarios. Nine months later the same respondents were invited to participate in a genuine data donation study. The results show that the correlation between willingness and actual donation was moderate ( $$\eta$$ : 0.28). Additionally, the determinants of self-reports and sharing behavior did not overlap. The willingness to donate was more strongly associated with softer attitudinal variables, whereas actual data sharing was linked more closely to harder demographic variables. These findings challenge the predictive validity of willingness to share measures and highlight the need for realistic scenarios in survey experiments, minimizing participants’ perceived risks of the task in question, and addressing social desirability bias.

Infant EEG microstate dynamics relate to fine-grained patterns of infant attention during naturalistic play with caregivers

As infants grow, they develop greater attentional control during interactions with others, shifting from patterns of attention primarily driven by caregivers (exogenous) to those that are also self-directed (endogenous). The ability to endogenously control attention during infancy is thought to reflect ongoing brain development and is influenced by patterns of joint attention between infant and caregiver. However, whether measures of infant attentional control and caregiver behavior during infant–caregiver interactions relate to patterns of infant brain activity is unknown and key for informing developmental models of attentional control. Using data from 43 infant–caregiver dyads, we quantified patterns of visual attention with dyadic, head-mounted eye tracking during infant–caregiver play and associated them with the duration of infant EEG microstate D/4 measured during rest. Importantly, microstate D/4 is a scalp potential topography thought to reflect the organization and function of attention-related brain networks. We found that microstate D/4 associated positively with infant-led joint attention rate but did not associate with caregiver-led joint attention rate, suggesting that infant-led coordination of joint attention during play may be critical for the neurobiological development of attentional control, or vice versa. Further, we found that microstate D/4 associated negatively with infant attention shift rate and positively with infant sustained attention duration, suggesting that increased stability of microstate D/4 may reflect maturation of attentional control and its underlying neural substrates. Together, our findings provide insights into how infant attentional control abilities and infant–caregiver visual behavior during play are associated with the spatial and temporal dynamics of infant brain activity.

Giant Rashba splitting in PtTe/PtTe2 heterostructure

Abstract Achieving a large spin splitting is highly desirable for spintronic devices, which often requires breaking of the inversion symmetry. However, many atomically thin films are centrosymmetric, making them unsuitable for spintronic applications. Here, we report a strategy to achieve inversion symmetry breaking from a centrosymmetric transition metal dichalcogenide (TMDC) bilayer PtTe2, leading to a giant Rashba spin splitting. Specifically, the thermal annealing turns one layer of PtTe2 sample into a transition metal monochalcogenide (TMMC) PtTe through Te extraction, thus forming PtTe/PtTe2 heterostructure with inversion symmetry breaking. In this naturally-formed PtTe/PtTe2 heterostructure, we observe a giant Rashba spin splitting with Rashba coefficient of α R  = 1.8 eV ⋅ Å, as revealed by spin- and angle-resolved photoemission spectroscopy measurements. Our work demonstrates a convenient and effective pathway for achieving pronounced Rashba splitting in centrosymmetric TMDC thin films by creating TMMC/TMDC heterostructure, thereby extending their potential applications to spintronics.

Genome-wide characterization and expression profiling of MADS-box family genes during organ development and drought stress in Camelina sativa L

Positive effects of species mixing on biodiversity of understory plant communities and soil health in forest plantations

Mixed-species plantations are increasingly recognized for their potential to maintain forest biodiversity and soil health; however, a comprehensive assessment of their global effectiveness is lacking. To fill this knowledge gap, we conducted a meta-analysis of 7,045 paired observations between mixed-species and monoculture plantations, derived from 311 studies across diverse forest ecosystems worldwide. Our results show that mixed-species plantations significantly increased understory plant biomass, cover, and species richness by 32.6%, 55.4%, and 32.2%, respectively, compared to monocultures. Furthermore, the Shannon and Pielou diversity indices increased by 28.2% and 8.6%, respectively, and the Simpson index increased by 9.6%. When understory shrub and herbaceous species were considered separately, species mixing had significantly positive effects on shrub diversity but had no effect on herbaceous diversity. Moreover, mixed-species plantations markedly improved soil physical and chemical properties compared to monocultures. These improvements include increases in soil nutrient content (9.6 to 17.8%) and nutrient availability (14.7 to 33.5%), soil microbial biomass (17.2 to 28.8%), and soil carbon sequestration (7.2 to 19.9%). These enhancements were particularly pronounced in plantations that included legumes. Our findings reveal that the benefits of species mixing are influenced by climatic conditions, geographic location, and stand age, with the most substantial effects observed in temperate regions and mature stands. This study underscores the critical role of mixed-species plantations in promoting sustainable forest management and mitigating the ecological limitations of monocultures.

Complement-mediated enhancement of SARS-CoV-2 antibody neutralisation potency in vaccinated individuals

Abstract With the continued emergence of SARS-CoV-2 variants and concerns of waning immunity, there is a need for better defined correlates of protection to aid future vaccine and therapeutic developments. Whilst neutralising antibody titres are associated with protection, these are typically determined in the absence of the complement system, which has the potential to enhance neutralisation titres and strengthen correlates with protection in vivo. Here we show that replenishment of the complement system in neutralisation assays can significantly enhance neutralisation titres, with up to an ~83-fold increase in neutralisation of the BA.1.1.529 strain using cross-reactive sera from vaccination against the ancestral strain. The magnitude of enhancement significantly varies between individuals, viral strains (wild-type/VIC01 and Omicron/BA.1), and cell lines (Vero E6 and Calu-3), and is abrogated following heat-inactivation of the complement source. Utilising ACE2 competition assays, we show that the mechanism of action is partially mediated by reducing ACE2-spike interactions. Through the addition of compstatin (a C3 inhibitor) to live virus neutralisation assays, the complement protein C3 is shown to be required for maximum efficiency. These findings further our understanding of SARS-CoV-2 immunity and neutralisation, with implications for protection against emerging variants and assessing future vaccine and therapeutic developments.

Association of waist circumference with all cause mortality in Parkinson’s disease

Asymmetric bending boundary layer: The <i>λ</i> -test

We investigate the mechanics of two asymmetric ribbons bound at one end and pulled apart at the other ends. We characterize the elastic junction near the bonding and conceptualize it as a bending boundary layer. While the size of this junction decreases with the pulling force, we observe the surprising existence of the binding angle as a macroscopic signature of the bending stiffnesses. Our results thus challenge the standard assumption of neglecting bending stiffness of thin shells at large tensile loading. In addition, we show how the rotational response of the structure exhibits a nonlinear and universal behavior regardless of the ratio of asymmetry. Leveraging the independence of the binding angle to the pulling force, we finally introduce the λ -test—a visual measurement technique to characterize membranes through simple mechanical coupling.

An epidermal serine sensing system for skin healthcare

Stand-alone MRI tool for semiautomatic volumetry of abdominal adipose compartments in patients with obesity

Abstract Abdominal adipose tissue (AT) amounts are increasingly considered as potential biomarkers for a variety of diseases and clinical questions, for instance, in diabetology, oncology or cardiovascular medicine. Despite the emergence of automated deep-learning methods for tissue quantification, interactive (supervised) segmentation tools will typically be used for model training. In comparison with CT-based approaches, MRI segmentation tools are more complex and less common. This work aims to validate a novel MRI-based tissue volumetry against a reference method in patients with (pre-) obesity. The new tool (segfatMR) was developed under a Matlab-based, open-source software framework and combines fast automatic pre-segmentation followed by manual (expert) corrections where needed. Analyses were performed retrospectively on a subset of clinical research MRI datasets (1.5 T Achieva XR, Philips Healthcare) and involved the segmentation of datasets from 20 patients (10 women/men) aged 25.1–63.1 (mean 48.5) years with BMIs between 28.3 and 58.8 (mean 36.8) kg/m2. Two independent expert readers analyzed the abdominopelvic data (30–40 slices, mean 35.8) with segfatMR and a widely used commercial tool (sliceOmatic). Coefficients of determination (R 2), bias and limits of agreement (Bland Altman) were determined. Segmentation performance (R 2 between methods) was excellent for both readers for SAT (&gt; 0.99) and very high for VAT (around 0.90). The novel method was almost twice as fast as the reference standard – 25 and 19 s/slice (R1 and R2) vs. 40 and 34 s/slice. The presented semiautomatic segmentation tool enables a fast and accurate quantification of whole abdominopelvic adipose tissue volume in obesity studies. Use, adjustments and extensions of the MRI volumetry tool are facilitated by the open-source design on a standard PC.

Diverse ancestral representation improves genetic intolerance metrics

Abstract The unprecedented scale of genomic databases has revolutionized our ability to identify regions in the human genome intolerant to variation—regions often implicated in disease. However, these datasets remain constrained by limited ancestral diversity. Here, we analyze whole-exome sequencing data from 460,551 UK Biobank and 125,748 Genome Aggregation Database (gnomAD) participants across multiple ancestries to test several key intolerance metrics, including the Residual Variance Intolerance Score (RVIS), Missense Tolerance Ratio (MTR), and Loss-of-Function Observed/Expected ratio (LOF O/E). We demonstrate that increasing ancestral representation, rather than sample size alone, critically drives their performance. Scores trained on variation observed in African and Admixed American ancestral groups show higher resolution in detecting haploinsufficient and neurodevelopmental disease risk genes compared to scores trained on European ancestry groups. Most strikingly, MTR trained on 43,000 multi-ancestry exomes demonstrates greater predictive power than when trained on a nearly 10-fold larger dataset of 440,000 non-Finnish European exomes. We further find that European ancestry group-based scores are likely approaching saturation. These findings highlight the need for enhanced population representation in genomic resources to fully realize the potential of precision medicine and drug discovery. Ancestry group-specific scores are publicly available through an interactive portal: http://intolerance.public.cgr.astrazeneca.com/ .