Alternative splicing has been shown to participate in tumor progression, including hepatocellular carcinoma. The poor prognosis of patients with HCC calls for molecular classification and biomarker identification to facilitate precision medicine. We performed ssGSEA analysis to quantify the pathway activity of RNA splicing in three HCC cohorts. Kaplan–Meier and Cox methods were used for survival analysis. GO and GSEA were performed to analyze pathway enrichment. We confirmed that RNA splicing is significantly correlated with prognosis, and identified an alternative splicing-associated protein LUC7L3 as a potential HCC prognostic biomarker. Further bioinformatics analysis revealed that high LUC7L3 expression indicated a more progressive HCC subtype and worse clinical features. Cell proliferation-related pathways were enriched in HCC patients with high LUC7L3 expression. Consistently, we proved that LUC7L3 knockdown could significantly inhibit cell proliferation and suppress the activation of associated signaling pathways in vitro. In this research, the relevance between RNA splicing and HCC patient prognosis was outlined. Our newly identified biomarker LUC7L3 could provide stratification for patient survival and recurrence risk, facilitating early medical intervention before recurrence or disease progression. Full article

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC. Full article

With the discovery of tyrosine kinase inhibitors (TKIs), overall survival in patients with chronic myeloid leukemia (CML) now approaches that of the general population. While these TKIs have proven to be lifesaving, remaining on them lifelong creates both physical and financial burdens for patients. Recently, multiple trials have begun looking into the efficacy of trialing patients off these TKIs to see if they can sustain treatment-free remission (TFR). TFR eligibility is currently limited to a small population of patients with both robust and sustained responses to TKIs. Currently, for those who attempt a trial of TFR, the average success rates are promising, with anywhere from 38 to 54% of patients experiencing sustained TFR. For those who fail to maintain sustained TFR, safety results to date are reassuring, with almost all patients successfully responding to the re-initiation of TKIs, with death and disease progression being very rare complications. Moving forward, research is being conducted to more accurately risk stratify patients at diagnosis and pair them with optimized upfront treatment regimens aimed at increasing candidacy for the trial of TFR. Full article

Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver—MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis—MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C. Full article

With the continuous development of rural revitalization and urbanization in China, the sustainable transformation of traditional rural architecture has become increasingly important. This study takes the Thangka exhibition hall in rural Malkang, Sichuan Province, as the research object and proposes a Thangka exhibition hall architectural design centered around solar heating and aiming for near-zero energy consumption. The research method involves establishing a solar energy system model on the roof of the exhibition hall and utilizing solar angle and area calculation formulas along with simulation software to calculate the optimal installation angle and area of solar panels, with the aim of achieving indoor temperatures that meet Thangka protection requirements while achieving zero-energy heating. Preliminary results indicate that this solar-centric near-zero energy architectural design can effectively promote the increase in indoor temperature through solar thermal conversion. Additionally, through calculation and simulation, the optimal installation angle for the solar panels achieving zero-energy heating is determined to be 24.25 with an azimuth angle of −1.2. The optimum installation area for solar panels is 8.2 square meters in the showroom and 2.7 square meters in the storeroom. Among these, the solar panel area for the Thangka exhibition hall constitutes 4.12% of the total area and is required for maintaining Thangka protection temperature requirements throughout the year, while the solar panel area for the storage room constitutes 1.88% and is also needed for the same purpose. Studying the optimal installation angle and area of solar panels can transform the exhibition hall into a near-zero-energy building, meeting the temperature requirements for Thangka preservation and human thermal comfort, while also achieving optimal economic benefits. This provides guidance and a reference for promoting near-zero-energy buildings in rural areas. Full article

Plant extracts can be a valuable source of biologically active compounds in many cosmetic preparations. Their effect depends on the phytochemicals they contain and their ability to penetrate the skin. Therefore, in this study, the possibility of skin penetration by phenolic acids contained in dogwood extracts of different fruit colors (yellow, red, and dark ruby red) prepared using different extractants was investigated. These analyses were performed using a Franz chamber and HPLC-UV chromatography. Moreover, the antioxidant properties of the tested extracts were compared and their impact on the intracellular level of free radicals in skin cells was assessed. The cytotoxicity of these extracts towards keratinocytes and fibroblasts was also analyzed and their anti-inflammatory properties were assessed using the enzyme-linked immunosorbent assay (ELISA). The analyses showed differences in the penetration of individual phenolic acids into the skin and different biological activities of the tested extracts. None of the extracts had cytotoxic effects on skin cells in vitro, and the strongest antioxidant and anti-inflammatory properties were found in dogwood extracts with dark ruby red fruits. Full article

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 μg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin’s bioactivity mirrored the extract’s effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low μM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract’s biological activities. This study is the first to explore ellagitannins’ potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies. Full article

This research work is based on a previous study by the authors that characterized the behavior of FBG sensors with a polyimide coating in a structural monitoring system. Sensors applied to structural health monitoring are affected by the presence of simultaneous multidirectional strains. The previous study observed the influence of the transverse strain (${\epsilon }_y$) while keeping the longitudinal strain constant (${\epsilon }_x$), where the x direction is the direction of the optical fiber. The present study develops an experimental methodology consisting of a biaxial test plan on cruciform specimens with three embedded FBG sensors coated with polyimide, acrylate, and ORMOCER^®. Applying the Strain–Optic Theory as a reference, a comparison of the experimental values obtained with the different coatings was studied. This experimental work made it possible to study the influence of the transverse strain (${\epsilon }_y$) on the longitudinal measurements of each FBGS and the influence of the coating material. Finally, the calibration procedure was defined as well as $K$ (strain sensitivity factor) for each sensor. Full article

China faces severe water resource shortages due to the uneven distribution of water resources and ever-increasing water demand driven by rapid industrialization and urbanization. The virtual water trade (VWT) is a potential solution to conserve water resources by transferring water from water-abundant/water-productive regions to water-scarce/less water-productive regions. Based on the inter-provincial input-output model, the provincial VWT of China was estimated at the sectoral level. The relationship of VWT with water resources in 30 provinces was analyzed in relation to the water stress index (WSI). It was found that (1) total inter-provincial VW trade showed a downward trend during the study period, with 363.91 km³ in 2002, 283.72 km³ in 2007, and 285.23 km³ in 2012. Overall, the primary industry dominated the VWT for most provinces. (2) China’s virtual water flowed from the relatively underdeveloped central and western regions to the east with a relatively developed economy from the inter-provincial level. This trend became increasingly prominent. (3) In many instances, VW was transferred from water-poor to water-rich areas. These results imply that China needs to improve its water use efficiency and optimize its regional industrial structure. Additionally, establishing an ecological compensation mechanism is considered a valuable measure for China to alleviate regional water resource pressure. Full article

Background: Sleep quality is known to affect automatic and executive brain functions such as gait control and cognitive processing. This study aimed to investigate the effect of dual tasks on gait spatiotemporal parameters among young adults with good and poor sleep quality. Methods: In total, 65 young adults with a mean age of 21.1 ± 2.5 were assessed for gait analysis during single-task and dual-task conditions. The participants’ sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and gait was assessed using the BTS Gaitlab System. The participants were asked to walk at natural speed as a single-task condition, followed by walking while performing a cognitive task as a dual-task condition. The parameters assessed included the gait velocity (m/s), cadence (steps/min), step width (m), and stride length (m). The dual-task cost (DTC) on each gait parameter was calculated. The Mann–Whitney U test was used to compare the differences in the DTC on gait variables between the good and poor sleep quality groups and the Spearman correlation test was used to assess the correlation between total PSQI scores and the DTC. Results: At a significance level of p < 0.05, a significant difference in cadence between the two sleep quality groups was observed, in addition to a positive correlation between sleep quality and the DTC effect on gait mean velocity, cadence, and stride length. Our findings also revealed a greater DTC in participants with poorer sleep quality. Conclusions: These findings contribute to our perception of the significance of sleep quality in gait performance while multitasking in younger populations. Full article

Science has been an incredibly powerful and revolutionary force. However, it is not clear whether science is suited to performance under pressure; generally, science achieves best in its usual comfort zone of patience, caution, and slowness. But, if science is organized knowledge and acts as a guiding force for making informed decisions, it is important to understand how science and scientists perform as a reliable and valuable institution in a global crisis. This paper provides insights and reflections based on the experience of the COVID-19 pandemic and from an analytical perspective. In particular, we analyze aspects such as speed, transparency, trust, data sharing, scientists in the political arena, and the psychology of scientists—all of which are areas inviting more detailed investigations by future studies conducting systematic empirical studies. Full article

The binary nature of life is deeply ingrained in daily experiences, evident in the stark distinctions between life and death and the living and the inert. While this binary perspective aligns with disciplines like medicine and much of biology, uncertainties emerge in fields such as microbiology, virology, synthetic biology, and systems chemistry, where intermediate entities challenge straightforward classification as living or non-living. This contribution explores the motivations behind both binary and non-binary conceptualizations of life. Despite the perceived necessity to unequivocally define life, especially in the context of origin of life research and astrobiology, mounting evidence indicates a gray area between what is intuitively clearly alive and what is distinctly not alive. This prompts consideration of a gradualist perspective, depicting life as a spectrum with varying degrees of “lifeness”. Given the current state of science, the existence or not of a definite threshold remains open. Nevertheless, shifts in epistemic granularity and epistemic perspective influence the framing of the question, and scientific advancements narrow down possible answers: if a threshold exists, it can only be at a finer level than what is intuitively taken as living or non-living. This underscores the need for a more refined distinction between the inanimate and the living. Full article

In the field of maritime traffic management, overcoming the challenges of low prediction accuracy and computational inefficiency in ship trajectory prediction is crucial for collision avoidance. This paper presents an advanced solution using a deep bidirectional long- and short-term memory network (BILSTM) and the Optuna hyperparameter automatic optimized framework. Utilizing automatic identification system (AIS) data to analyze ship navigation patterns, the study applies Optuna to fine-tune the hyperparameters of the BILSTM network to improve prediction accuracy and efficiency. The developed Optuna–BILSTM model shows a remarkable 7% increase in prediction accuracy over traditional back propagation (BP) neural networks and standard BILSTM models. These results not only improve ship navigation and safety but also have significant implications for the development of autonomous ship collision avoidance systems, marking a significant step toward safer and more efficient maritime traffic management. Full article

Lactic acid bacteria Ligilactobacillus salivarius has been shown to be a substitute for antibiotics in the treatment of bacterial disease in high animals. However, its beneficial mechanism in fish farming is still unclear. This study evaluated the antagonistic effects of the Ligilactobacillus salivarius GX118 strain on Aeromonas salmonicida and its regulation of rainbow trout growth in vivo and in vitro. The results found that GX118 produces an antibacterial substance that can directly destroy the cell wall of A. salmonicida. Whole-genome sequencing of GX118 revealed that Enterolysin A is a type III bacteriocin with antibacterial properties. An in vivo experiment showed that the supplementation of GX118 in diet competitively inhibited the colonization of A. salmonicida in the intestine. In addition, it was able to improve the growth performance of rainbow trout within a 21-day feeding experiment. The supplementation of GX118 increased the diversity of gut microbiota, in which the abundance of Bacteroidota, Blautia, and Rhodobacteraceae increased. In addition, the use of GX118 activated the expression of IFN-γ and NF-κB genes and reduced the expression level of IL-6 and IL-8, thus exhibiting a certain effect on activating the immunity of rainbow trout. This study provides a scientific basis for the development of antibacterial probiotics in the healthy farming of rainbow trout. Full article

Background: The advancement of multidisciplinary treatment has increased the need to develop tests to monitor tumor burden during treatment. We herein analyzed urinary microRNAs within extracellular vesicles from patients with esophageal squamous cell carcinoma (ESCC) and normal individuals using a microarray. Methods: Patients with advanced ESCC who underwent esophagectomy (A), endoscopic submucosal resection (ESD) (B), and healthy donors (C) were included. Based on microRNA expression among the groups (Analysis 1), microRNAs with significant differences between groups A and C were selected (Analysis 2). Of these candidates, microRNAs in which the change between A and C was consistent with the change between B and C were selected for downstream analysis (Analysis 3). Finally, microRNA expression was validated in patients with recurrence from A (exploratory analysis). Results: For analysis 1, 205 microRNAs were selected. For Analyses 2 and 3, the changes in 18 microRNAs were consistent with changes in tumor burden as determined by clinical imaging and pathological findings. The AUC for the detection of ESCC using 18 microRNAs was 0.72. In exploratory analysis, three of eighteen microRNAs exhibited a concordant trend with recurrence. Conclusions: The current study identified the urinary microRNAs which were significantly expressed in ESCC patients. Validation study is warranted to evaluate whether these microRNAs could reflect tumor burden during multidisciplinary treatment for ESCC. Full article

Diacylhydrazine is thermally and chemically stable, and it remains inert to oxygen even at high temperatures. However, it is rapidly oxidized by sodium hypochlorite, leading to its decomposition into carboxylic acid and nitrogen gas. In the synthesis of a novel poly(diacylhydrazine) as an oxidatively degradable polymer, L-leucine methyl ester is acylated by terephthaloyl chloride. Subsequent hydrazination yields a bishydrazide monomer. The oxidative coupling polymerization of this monomer produces poly(diacylhydrazine). The molecular structures of the products are confirmed by an ¹H NMR analysis. A polymodal molecular weight distribution and a large polydispersity index are observed by GPC in all cases. A 10% weight loss temperature is noted at 286 °C in air by TGA. The obtained polymer is not oxidized by oxygen. No glass transition is observed below the decomposition temperature. Upon the treatment of the poly(diacylhydrazine) with sodium hypochlorite solution, decomposition occurs rapidly, resulting in monomeric carboxylic acid and nitrogen gas. The L-leucine-based poly(diacylhydrazine) serves as a novel on-demand degradable polymer with high levels of thermal and chemical stability during usage. Full article

In this paper, the global distribution of precipitation for 2023, in terms of global totals and regional anomaly patterns, is analyzed using information from the new Global Precipitation Climatology Project (GPCP) V3.2 Monthly product, including how the precipitation amounts and patterns from 2023 fit into the longer record from 1983–2023. The tropical pattern of anomalies for 2023 is dominated by the effect of the El Nino which began during the Northern Hemisphere spring, after three plus years of La Nina conditions. The transition from La Nina conditions through 2022 shows the rapid change in many regional features from positive to negative anomalies or the reverse. Comparison of the observed regional trend maps with climate model results indicates similarity between the observations and the model results forced by observed SSTs, while the “free-running” model ensemble shows only a broad general agreement over large regions. Global total precipitation shows about a 3% range over the span of data, with El Nino and La Nina years prominent as positive and negative features, with 2023 showing a small positive global anomaly. The ITCZ (Inter-Tropical Convergence Zone) latitude band, 0–10° N, sets a record high mean rain rate in 2023 after a steady upward trend over the decades, probably a response related to global warming. Full article

Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition. Full article

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes. Full article

(1) Background: Renal-cell carcinoma (RCC) incidence has been steadily rising, with obesity identified as a potential risk factor. However, the relationship between obesity and RCC prognosis remains unclear. This systematic review aims to investigate the impact of different adipose tissue measurements on RCC behavior and prognosis. (2) Methods: A search of MEDLINE databases identified 20 eligible studies focusing on various fat measurements, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PRAT), and the Mayo adhesive probability (MAP) score. (3) Results: The review revealed conflicting findings regarding the association between adipose tissue measurements and RCC outcomes. While some studies suggested a protective role of certain fat deposits, particularly VAT, against disease progression and mortality, others reported contradictory results across different adipose metrics and RCC subtypes. (4) Conclusions: Methodological variations and limitations, such as retrospective designs and sample size constraints, pose challenges to standardization and generalizability. Further research is needed to understand these associations better and establish standardized approaches for adiposity assessment in RCC patients, which could inform clinical practice and therapeutic decision-making. Full article

We aimed to analyze the association between CYP7B1 and prostate cancer, along with its association with proteins involved in cancer and metabolic processes. A retrospective analysis was performed on 390 patients with prostate cancer (PC) or benign prostatic hyperplasia (BPH). We investigated the interactions between CYP7B1 expression and proteins associated with PC and metabolic processes, followed by an analysis of the risk of biochemical recurrence based on CYP7B1 expression. Of the 139 patients with elevated CYP7B1 expression, 92.8% had prostate cancer. Overall, no increased risk of biochemical recurrence was associated with CYP7B1 expression. However, in a non-diabetic subgroup analysis, higher CYP7B1 expression indicated a higher risk of biochemical recurrence, with an HR of 1.78 (CI: 1.0–3.2, p = 0.05). PC is associated with elevated CYP7B1 expression. In a subgroup analysis of non-diabetic patients, elevated CYP7B1 expression was associated with an increased risk of biochemical recurrence, suggesting increased cancer aggressiveness. Full article

Cancer, with its complexity and numerous origins, continues to provide a huge challenge in medical research. Anticancer peptides are a potential treatment option, but identifying and synthesizing them on a large scale requires accurate prediction algorithms. This study presents an intuitive classification strategy, named ACP-LSE, based on representation learning, specifically, a deep latent-space encoding scheme. ACP-LSE can demonstrate notable advancements in classification outcomes, particularly in scenarios with limited sample sizes and abundant features. ACP-LSE differs from typical black-box approaches by focusing on representation learning. Utilizing an auto-encoder-inspired network, it embeds high-dimensional features, such as the composition of g-spaced amino acid pairs, into a compressed latent space. In contrast to conventional auto-encoders, ACP-LSE ensures that the learned feature set is both small and effective for classification, giving a transparent alternative. The suggested approach is tested on benchmark datasets and demonstrates higher performance compared to the current methods. The results indicate improved Matthew’s correlation coefficient and balanced accuracy, offering insights into crucial aspects for developing new ACPs. The implementation of the proposed ACP-LSE approach is accessible online, providing a valuable and reproducible resource for researchers in the field. Full article