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There is little evidence in the literature about the relationship between frailty and falls in older adults. Our objective was to explore the relationship between frailty and falls, and to analyze the effect factors (e.g., gender, different frailty assessment tools, areas, level of national economic development, and year of publication) of the association between frailty and falls among older adults. Systematic review and meta-analysis. Cohort studies that evaluated the association between frailty and falls in the older adults were included. We excluded any literature outside of cohort studies. We did a systematic literature search of English databases PubMed, Scopus, Web of Science, EBSCOhost, and SciElO, as well as the Chinese databases CNKI, WANFANG, and VIP from 2001 until October 2022. The eligible studies were evaluated for potential bias using the Newcastle-Ottawa Scale (NOS). Study selection, data extraction and assessment of study quality were each conducted by two investigators. In Stata/MP 17.0 software, we calculated pooled estimates of the prevalence of falls by using a random-effects model, Subgroup analysis was conducted based on gender, different frailty assessment tools, areas, level of economic development, and year of publication. The results are presented using a forest plot. Twenty-nine studies were included in this meta-analysis and a total of 1,093,270 participants aged 65 years and above were enrolled. Among the older adults, frailty was significantly associated with a higher risk for falls, compared with those without frailty (combined RR-relative risk = 1.48, 95% CI-confidence interval: 1.27–1.73, I2=98.9%). In addition, the results of subgroup analysis indicated that men had a higher risk for falls than women among the older adults with frailty (RR 1.94, 95% CI: 1.18–3.2 versus RR 1.44, 95% CI: 1.24–1.67). Subgroup analysis by different frailty assessment tools revealed an increased risk of falls in older adults with frailty when assessed using the Frailty Phenotype (combined RR 1.32, 95%CI: 1.17–1.48), FRAIL score (combined RR 1.82, 95%CI: 1.36–2.43), and Study of Osteoporotic Fractures index (combined RR 1.54, 95%CI: 1.10–2.16). Furthermore, subgroup analysis by areas and level of national economic development found the highest fall risk in Oceania (combined RR 2.35, 95%CI: 2.28–2.43) and the lowest in Europe (combined RR 1.20, 95%CI: 1.05–1.38). Developed countries exhibited a lower fall risk compared to developing countries (combined RR 1.44, 95%CI: 1.21–1.71). Analysis by year of publication showed the highest fall risk between 2013–2019 (combined RR 1.79, 95%CI: 1.45–2.20) and the lowest between 2001–2013 (combined RR 1.21, 95%CI: 1.13–1.29). Frailty represents a significant risk factor for falls in older adults, with the degree of risk varying according to the different frailty assessment tools employed, and notably highest when using the FRAIL scale. Additionally, factors such as gender, areas, level of national economic development, and healthcare managers' understanding of frailty may all impact the correlation between frailty and falls. Thus, it's imperative to select suitable frailty diagnostic tools tailored to the specific characteristics of the population in question. This, in turn, facilitates the accurate identification of frailty in older adults and informs the development of appropriate preventive and therapeutic strategies to mitigate fall risk.

Superconductivity in the cuprates is found to be intertwined with charge and spin density waves. Determining the interactions between the different types of order is crucial for understanding these important materials. Here, we elucidate the role of the charge density wave (CDW) in the prototypical cuprate La 1.885 Sr 0.115 CuO 4 , by studying the effects of large magnetic fields ( H ) up to 24 Tesla. At low temperatures ( T ), the observed CDW peaks reveal two distinct regions in the material: a majority phase with short-range CDW coexisting with superconductivity, and a minority phase with longer-range CDW coexisting with static spin density wave (SDW). With increasing magnetic field, the CDW first grows smoothly in a manner similar to the SDW. However, at high fields we discover a sudden increase in the CDW amplitude upon entering the vortex-liquid state. Our results signify strong coupling of the CDW to mobile superconducting vortices and link enhanced CDW amplitude with local superconducting pairing across the H  −  T phase diagram. Superconductivity in the cuprates is known to be intertwined with charge and spin density waves. Here, the authors study the prototypical cuprate La 1.885 Sr 0.115 CuO 4 via x-ray scattering and discover a sudden increase in the charge-density-wave amplitude upon entering the superconducting-vortex-liquid state at high magnetic field.

Background Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. Main body of the abstract We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn’s Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future. Short conclusion MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs’ efficacy.

SummaryThe aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of balloon kyphoplasty (BK), percutaneous vertebroplasty (PVP), and non-surgical treatment (NST) for patients with osteoporotic vertebral compression fractures (OVCFs). The results demonstrate that for pain and functional status, PVP was significantly better than NST, while the three treatments did not significantly differ in other outcomes.IntroductionBK, PVP, and NST are widely used to treat OVCFs, but preferable treatment is unknown. The aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of BK, PVP, and NST for patients with OVCFs.MethodsPubMed, EMBASE, and the Cochrane Library were screened. Based on the preplanned eligibility criteria, we screened and included randomized controlled trials that compared BK, PVP, and NST in treating patients with OVCFs. The risk of bias for individual studies was appraised. The data were pooled using a Bayesian network meta-analysis and a traditional direct comparison meta-analysis.ResultsOf the 1057 relevant studies, 15 were eligible and included. Compared with NST, PVP significantly reduced pain, Oswestry Disability Index (ODI), and Roland–Morris Disability Questionnaire (RMDQ). The comparative efficacy of BK and PVP was similar for pain (mean difference (MD) 0.51, 95% credible interval (CrI) − 0.35 to 1.4), ODI (MD 0.11, 95% CrI − 13 to 13), and RMDQ (MD 1.2, 95% CrI − 2.7 to 5.4). The European Quality of Life–5 Dimensions (EQ–5D) and Physical Component Summary subscales of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36 PCS) did not differ significantly. There were also no substantial differences in the risks of subsequent vertebral fractures, adjacent vertebral fractures, and re-fractures at the treated level across all comparators. The results of pairwise meta-analyses were almost consistent with those of network meta-analyses. The treatment ranking indicated that PVP had the highest probability of being the most effective for pain, ODI, RMDQ, and EQ-5D. BK had the highest probability of improving SF-36 PCS and of reducing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST was ranked first in preventing adjacent vertebral fractures.ConclusionPVP was the most effective method for improving pain, functional status, and quality of life (based on EQ-5D). BK emerged as the best intervention for decreasing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST could be ranked first in reducing adjacent vertebral fractures. The future directions of OVCFs treatment will depend on the outcomes of additional and larger randomized trials in comparing BK with PVP.

Malaria is caused by eukaryotic Plasmodium spp. parasites that classically infect red blood cells. These are difficult organisms to investigate genetically because of their AT-rich genomes. Zhang et al. have exploited this peculiarity by using piggyBac transposon insertion sites to achieve saturation-level mutagenesis for identifying and ranking essential genes and drug targets (see the Perspective by White and Rathod). Genes that are current candidates for drug targets were identified as essential, in contrast to many vaccine target genes. Notably, the proteasome degradation pathway was confirmed as a target for developing therapeutic interventions because of the several essential genes involved and the link to the mechanism of action of the current frontline drug, artemisinin. Science , this issue p. eaap7847 ; see also p. 490 Mutagenesis of a human malaria parasite reveals a core set of genes essential for asexual growth in red blood cells in vitro. Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Despite decades of research, the distinct biology of these parasites has made it challenging to establish high-throughput genetic approaches to identify and prioritize therapeutic targets. Using transposon mutagenesis of P. falciparum in an approach that exploited its AT-rich genome, we generated more than 38,000 mutants, saturating the genome and defining mutability and fitness costs for over 87% of genes. Of 5399 genes, our study defined 2680 genes as essential for optimal growth of asexual blood stages in vitro. These essential genes are associated with drug resistance, represent leading vaccine candidates, and include approximately 1000 Plasmodium -conserved genes of unknown function. We validated this approach by testing proteasome pathways for individual mutants associated with artemisinin sensitivity.

Human life expectancy is significantly impacted by cancer, with liquid biopsy emerging as an advantageous method for cancer detection because of its noninvasive nature, high accuracy, ease of sampling, and cost-effectiveness compared with conventional tissue biopsy techniques. Liquid biopsy shows promise in early cancer detection, real-time monitoring, and personalized treatment for various cancers, including lung, cervical, and prostate cancers, and offers innovative approaches for cancer diagnosis and management. By utilizing circulating tumor DNA, circulating tumor cells, and exosomes as biomarkers, liquid biopsy enables the tracking of cancer progression. Various techniques commonly used in life sciences research, such as polymerase chain reaction (PCR), next-generation sequencing (NGS), and droplet digital PCR, are employed to assess cancer progression on the basis of different indicators. This review examines the latest advancements in liquid biopsy markers-circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes-for cancer diagnosis over the past three years, with a focus on their detection methodologies and clinical applications. It encapsulates the pivotal aims of liquid biopsy, including early detection, therapy response prediction, treatment monitoring, prognostication, and its relevance in minimal residual disease, while also addressing the challenges facing routine clinical adoption. By combining the latest research advancements and practical clinical experiences, this work focuses on discussing the clinical significance of DNA methylation biomarkers and their applications in tumor screening, auxiliary diagnosis, companion diagnosis, and recurrence monitoring. These discussions may help enhance the application of liquid biopsy throughout the entire process of tumor diagnosis and treatment, thereby providing patients with more precise and effective treatment plans.

Prostate cancer is prevalent among men aged 65 and older. Bone metastasis occurs in up to 90% of advanced prostate cancer patients, metastatic prostate cancer is generally considered a non-curative condition which can impact quality of life. The tumor microenvironment, comprising diverse cellular and non-cellular elements, interacts with prostate cancer cells to affect tumor growth and bone metastasis. Within the bone microenvironment, different cell types, including osteoblasts, osteoclasts, adipocytes, endothelial cells, hematopoietic stem cells, and immune cells, engage with tumor cells. Some cells alter tumor behavior, while others are impacted or overpowered by tumor cells, leading to different phases of tumor cell movement, dormancy, latency, resistance to treatment, and advancement to visible bone metastasis. This review summarizes recent research on the tumor microenvironment and bone microenvironment in prostate cancer bone metastasis, exploring underlying mechanisms and the potential value of targeting these environments for treatment.

Background: Chinese women tend to have small and dense breasts and ultrasound is a common method for breast cancer screening in China. However, its efficacy and cost comparing with mammography has not been evaluated in randomised trials. Methods: At 14 breast centres across China during 2008–2010, 13 339 high-risk women aged 30–65 years were randomised to be screened by mammography alone, ultrasound alone, or by both methods at enrolment and 1-year follow-up. Results: A total of 12 519 and 8692 women underwent the initial and second screenings, respectively. Among the 30 cancers (of which 15 were stage 0/I) detected, 5 (0.72/1000) were in the mammography group, 11 (1.51/1000) in the ultrasound group, and 14 (2.02/1000) in the combined group ( P =0.12). In the combined group, ultrasound detected all the 14 cancers, whereas mammography detected 8, making ultrasound more sensitive (100 vs 57.1%, P =0.04) with a better diagnostic accuracy (0.999 vs 0.766, P =0.01). There was no difference between mammography and ultrasound in specificity (100 vs 99.9%, P =0.51) and positive predictive value (72.7 vs 70.0%; P =0.87). To detect one cancer, the costs of ultrasound, mammography, and combined modality were $7876, $45 253, and $21 599, respectively. Conclusions: Ultrasound is superior to mammography for breast cancer screening in high-risk Chinese women.

Epithelial–mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis. Overexpression of miR-218 inhibited cell migration and invasion as well as the EMT process. Of particular importance, miR-218 was involved in the metastatic process of lung cancer cells in vivo by suppressing local invasion and distant colonization. We identified Slug and ZEB2 as direct functional targets of miR-218. Inverse correlations were observed between miR-218 levels and Slug/ZEB2 levels in cancer tissue samples. In addition, overexpression of miR-218 in H1299 increased chemosensitivity of cells to cisplatin treatment through suppression of Slug and ZEB2. These findings highlight an important role of miR-218 in the regulation of EMT-related traits and metastasis of lung cancer in part by modulation of Slug/ZEB2 signaling, and provide a potential therapeutic strategy by targeting miR-218 in NSCLC.

Our knowledge is still poor regarding the response of the precipitation vertical structure to aerosols, partly due to the ignorance of precipitation occurring at different spatial scales. A total of 6 years of collocated ground-based PM10 and satellite-based (Tropical Rainfall Measuring Mission, TRMM) radar data, along with ERA-Interim reanalysis, are used in this study to investigate the aerosol effects on three localized rain regimes (shallow, stratiform, and convective rain) over the Pearl River Delta region of China. A subjective analysis method is proposed to discriminate between the localized and synoptic-scale precipitations based on weather composite charts where daily averaged wind field at 850 hPa is overlaid with the geopotential height at 500 hPa. In general, average rain rate tends to be greater under polluted conditions than under clean conditions. But such potential aerosol effects are regime dependent: as the atmosphere becomes slightly polluted (PM10≤38 µg m−3), the top 1 % radar reflectivity (Z) for all regimes initially increases, followed by continued increases and weak decreases for convective and stratiform/shallow rain regimes, respectively. As the atmosphere becomes much more polluted, such regime dependences of aerosol effects are more significant. From a perspective of the vertical Z structure, comparisons between polluted conditions (days with the highest third of PM10 concentration) and clean conditions (days with the lowest third of PM10 concentration) show that the convective rain regime exhibits a deeper and stronger Z pattern, whereas a much shallower and weaker Z pattern is observed for stratiform and shallow precipitation regimes. In particular, the top height of the 30 dBZ rain echo increases by ∼29 % (∼1.27 km) for the convective regime, but decreases by ∼10.8 % (∼0.47 km) for the stratiform regime. However, no noticeable changes are observed for the shallow precipitation regime. Impacts of meteorological factors are further studied on both rain top height (RTH) and the center of gravity of Z, including vertical velocity, vertical wind shear, convection available potential energy, and vertically integrated moisture flux divergence (MFD). The possible invigoration effect on convective precipitation seems dependent on wind shear, in good agreement with previous findings. Overall, the observed dependence of the precipitation vertical structure on ground-based PM10 supports the notion of aerosol invigoration or suppression effect on cold or warm rain and adds new insights into the nature of the complex interactions between aerosol and various localized precipitation regimes.