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Chromosomal instability (CIN) is a hallmark of cancer aggressiveness, providing genetic plasticity and tumor heterogeneity that allows the tumor to evolve and adapt to stress conditions. CIN is considered a cancer therapeutic biomarker because healthy cells do not exhibit CIN. Despite recent efforts to identify therapeutic strategies related to CIN, the results obtained have been very limited. CIN is characterized by a genetic signature where a collection of genes, mostly mitotic regulators, are overexpressed in CIN‐positive tumors, providing aggressiveness and poor prognosis. We attempted to identify new therapeutic strategies related to CIN genes by performing a drug screen, using cells that individually express CIN‐associated genes in an inducible manner. We find that the overexpression of targeting protein for Xklp2 (TPX2) enhances sensitivity to the proto‐oncogene c‐Src (SRC) inhibitor dasatinib due to activation of the Yes‐associated protein 1 (YAP) pathway. Furthermore, using breast cancer data from The Cancer Genome Atlas (TCGA) and a cohort of cancer‐derived patient samples, we find that both TPX2 overexpression and YAP activation are present in a significant percentage of cancer tumor samples and are associated with poor prognosis; therefore, they are putative biomarkers for selection for dasatinib therapy. [ABSTRACT FROM AUTHOR]

Background: The efficacy of transcranial direct current stimulation (tDCS) has been studied extensively. The cathodic (c‐tDCS), anodic (a‐tDCS), and bihemispheric stimulation have demonstrated efficacy in the management of the paretic upper extremity (UE) after stroke, but it has not been determined which stimulation polarity has, so far, shown the best results. Objective: To evaluate the available evidence to determine which tDCS polarity has the best results in improving UE motor function after stroke. Methods: PubMed, PEDro, Web of Science, EMBASE, and SCOPUS databases were searched. Different Medical Subject Headings (MeSH) terms were combined for the search strategy, to cover all studies that performed a comparison between different tDCS configurations focused on UE motor rehabilitation in people with lived experience of stroke. Results: Fifteen studies remained for qualitative analysis and 12 for quantitative analysis. Non‐significant differences with a 95% confidence interval (CI) were obtained for c‐tDCS versus a‐tDCS (g = 0.10, 95% CI = −0.13; 0.33, p =.39, N = 292), for a‐tDCS versus bihemispheric (g = 0.02, 95% CI = −0.46; 0.42, p =.93, N = 81), and for c‐tDCS versus bihemispheric (g = 0.09, 95% CI = −0.84;.66, p =.73, N = 100). No significant differences between the subgroups of the meta‐analysis were found. Conclusions: The results of the present meta‐analysis showed no evidence that a stimulation polarity is superior to the others in the rehabilitation of UE motor function after stroke. A non‐significant improvement trend was observed toward c‐tDCS compared to a‐tDCS. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost‐effective technique for studying dementia globally, but lacks mechanistic models and produces non‐replicable results. METHODS: We developed a generative whole‐brain model that combines EEG source‐level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS: Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION: The results provide a novel agenda for developing mechanistic model‐inspired characterization and therapies in clinical, translational, and computational neuroscience settings. [ABSTRACT FROM AUTHOR]

The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present study, the microbiomes of saliva, crevicular fluid, feces, and non‐neoplastic and tumor intestinal tissue samples of 93 CRC patients and 30 healthy individuals without digestive disorders (non‐CRC) were analyzed by 16S rRNA metabarcoding procedures. The data revealed that Parvimonas, Fusobacterium, and Bacteroides fragilis were significantly over‐represented in stool samples of CRC patients, whereas Faecalibacterium and Blautia were significantly over‐abundant in the non‐CRC group. Moreover, the tumor samples were enriched in well‐known periodontal anaerobes, including Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella. Co‐occurrence patterns of these oral microorganisms were observed in the subgingival pocket and in the tumor tissues of CRC patients, where they also correlated with other gut microbes, such as Hungatella. This study provides new evidence that oral pathobionts, normally located in subgingival pockets, can migrate to the colon and probably aggregate with aerobic bacteria, forming synergistic consortia. Furthermore, we suggest that the group composed of Fusobacterium, Parvimonas, Bacteroides, and Faecalibacterium could be used to design an excellent noninvasive fecal test for the early diagnosis of CRC. The combination of these four genera would significantly improve the reliability of a discriminatory test with respect to others that use a single species as a unique CRC biomarker. [ABSTRACT FROM AUTHOR]

Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non‐CRC) were collected for microbiome analysis. Saliva (28 non‐CRC and 94 CRC), feces (30 non‐CRC and 97 CRC), subgingival fluid (20 CRC), and tumor tissue samples (20 CRC) were used for 16S metabarcoding and/or RNA sequencing (RNAseq) approaches. A differential analysis of the abundance, performed with the ANCOM‐BC package, adjusting the P‐values by the Holm‐Bonferroni method, revealed that Parvimonas was significantly over‐represented in feces from CRC patients (P‐value < 0.001) compared to healthy controls. A total of 11 Parvimonas micra isolates were obtained from the oral cavity and adenocarcinoma of CRC patients. Genome analysis identified a pair of isolates from the same patient that shared 99.2% identity, demonstrating that P. micra can translocate from the subgingival cavity to the gut. The data suggest that P. micra could migrate in a synergistic consortium with other periodontal bacteria. Metatranscriptomics confirmed that oral bacteria were more active in tumor than in non‐neoplastic tissues. We suggest that P. micra could be considered as a CRC biomarker detected in non‐invasive samples such as feces. [ABSTRACT FROM AUTHOR]

Background: Electroanatomical mapping is an essential tool in the ablation of typical AFL. Objectives: To identify the existence of voltage patterns in the CTI voltage maps and their relevance for typical AFL ablation. Methods: A voltage map of the CTI was made prior to ablation, identifying the areas of maximum voltage and their location along the CTI, allowing classification into patterns according to their distribution. A stepwise ablation approach targeting the areas of maximum voltage was conducted. The ablation characteristics were compared based on the pattern obtained. Results: Two voltage patterns were identified, with differences in ablation time to bidirectional CTI block. No complications occurred. Conclusions: Voltage mapping identifies patterns in the CTI with implications for typical AFL ablation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study examined the relationship between blood‐brain‐barrier permeability (BBBp), measured by cerebrospinal fluid/serum albumin ratio (QAlb), and cognitive decline progression in a clinical cohort. METHODS: This prospective observational study included 334 participants from the BIODEGMAR cohort. Cognitive decline progression was defined as an increase in Global Deterioration Scale and/or Clinical Dementia Rating scores. Associations between BBBp, demographics, and clinical factors were explored. RESULTS: Male sex, diabetes mellitus, and cerebrovascular burden were associated with increased log‐QAlb. Vascular cognitive impairment patients had the highest log‐QAlb levels. Among the 273 participants with valid follow‐up data, 154 (56.4%) showed cognitive decline progression. An 8% increase in the hazard of clinical worsening was observed for each 10% increase in log‐QAlb. DISCUSSION: These results suggest that increased BBBp in individuals with cognitive decline may contribute to clinical worsening, pointing to potential targeted therapies. QAlb could be a useful biomarker for identifying patients with a worse prognosis. [ABSTRACT FROM AUTHOR]

Background: Autosomal Dominant Alzheimer's disease (ADAD) is a subtype of AD in which the symptoms begin before age 65. ADAD is an important subtype of AD as it affects people at productive and reproductive age, has a genetic origin in most of the cases and is one of the 10 causes of years lost to disability (YDLs) (1). Colombia has the largest kindred family with ADAD due to PSEN1‐E280A genetic variant, we aimed to characterize the palliative care need in a subsample of individuals from these families. Methods: We performed an analytical observational study with one year follow‐up, data obtained from visit 1 (V1) is shown in this first report. Carriers of PSEN1‐E280A variant and GDS/FAST score above 4 were included. NECPAL and Edmonton surveys were conducted to the main carer to assess the need for palliative care and the frequency of symptoms. A complete medical evaluation was also performed. Results: 36 patients were included in V1. Median age was 53, most of the individuals were women (63.89%), lived in urban areas (88.89%) and the most common level of education was elementary‐middle school (47.22%). Clinical variables are listed in Table 2. Results of the poisson regression showed that dysphagia, pressure ulcers, asthenia perceived by the main carer, not being surprised if the patient died in the following 12 months (Surprise question of NECPAL scale), functional decline, use of medical services (2 visits in the past year), PAINAD scale and GDS/FAST scale were associated with the need for palliative care when adjusted by number of persons involved in caring, type of carer, hours of care per week and caregiver training. Conclusion: ADAD is a neurodegenerative disease that requires follow‐up by palliative care services. The health perception of the main carer should be taken into consideration when deciding the need for palliative care in these patients. [ABSTRACT FROM AUTHOR]

Objective: To review and synthesize existing evidence on the effectiveness of mirror therapy (MT) compared to active exercise‐based interventions (ie, cross‐training and conventional exercise) for reducing spasticity and sensory impairment in stroke survivors. Type: Systematic Review and Metanalysis. Literature Survey: Pubmed/MEDLINE, Cochrane, Embase, CINAHL, and Physiotherapy Evidence Database (PEDro), were searched. Methodology: Randomized controlled trials (RCTs) that investigated MT effectiveness in improving spasticity and sensory impairment in stroke survivors compared to a control group. Synthesis: Fifteen RCTs (653 volunteers) were included. Spasticity improvements achieved with MT were similar to those obtained with cross‐training (standard mean difference [SMD]: 0.12, 95% confidence interval [CI]: −0.43 to 0.68). In addition, when further combined with conventional exercise, spasticity improved similarly in both groups (SMD: 0.10, 95% CI: −0.16, 0.36). Lastly, when MT plus exercise was compared to exercise alone, spasticity decreased in both groups (SMD: 0.16, 95% CI: −0.16 to 0.48). Nevertheless, none of the Interventions seem effective on sensory impairment (SMD: 0.27, 95% CI: −0.28 to 0.81). Conclusions: MT is equally effective as other exercise therapies, such as cross‐training and conventional exercise, for improving spasticity in stroke survivors, whereas none of the explored interventions yielded beneficial effects on sensory impairment. Further well‐designed RCTs are needed to confirm the results. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Amyloid‐β (Aβ) and tau can be quantified in blood. However, biological factors can influence the levels of brain‐derived proteins in the blood. The blood‐brain barrier (BBB) regulates protein transport between cerebrospinal fluid (CSF) and blood. BBB altered permeability might affect the relationship between brain and blood biomarkers. METHODS: We assessed 224 participants in research (TRIAD, n = 96) and clinical (BIODEGMAR, n = 128) cohorts with plasma and CSF/positron emission tomography Aβ, p‐tau, and albumin measures. RESULTS: Plasma Aβ42/40 better identified CSF Aβ42/40 and Aβ‐PET positivity in individuals with high BBB permeability. An interaction between plasma Aβ42/40 and BBB permeability on CSF Aβ42/40 was observed. Voxel‐wise models estimated that the association of positron emission tomography (PET), with plasma Aβ was most affected by BBB permeability in AD‐related brain regions. BBB permeability did not significantly impact the relationship between brain and plasma p‐tau levels. DISCUSSION: These findings suggest that BBB integrity may influence the performance of plasma Aβ, but not p‐tau, biomarkers in research and clinical settings. HIGHLIGHTS: BBB permeability affects the association between brain and plasma Aβ levels.BBB integrity does not affect the association between brain and plasma p‐tau levels.Plasma Aβ was most affected by BBB permeability in AD‐related brain regions.BBB permeability increases with age but not according to cognitive status. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with familial early‐onset dementia (EOD) pose a unique opportunity for gene identification studies. METHODS: We present the phenotype and whole‐exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild‐type and mutant protein of the final candidate. RESULTS: Age at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss‐of‐function mechanism. DISCUSSION: This study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases. Highlights: A TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early‐onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease.TRIM25 protein studies support that the mutation exerts its effect through loss of function.TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration.The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research. [ABSTRACT FROM AUTHOR]

Background: A recent report estimates Latinos in the U.S. living with Alzheimer's Disease (AD) could reach as high as 3.5 million by 2060 and are 1.5 times more likely to develop AD than non‐Latino Whites. Consequently, Latino caregivers of people with Alzheimer's Disease or other related dementias (ADRD) face significant risks to their physical and mental well‐being. Due to the immense increase of ADRD in Latinos, it is important for research to highlight the ways in which caregivers can learn mindfulness based skills to support challenges they may face. Method: U.S. Latina caregivers of people with ADRD (n = 18) were analyzed from the CarePRO‐VS program. CarePRO‐VS is a multicomponent skill‐focused intervention conducted in Spanish that manages stress, tension and frustration associated with caregiving. This pilot project was conducted over ten weeks via telephone and Zoom including: (1) screening to determine eligibility, (2) pre‐ and post‐ intervention assessments conducted within approximately two weeks of the intervention, (3) individual "coach calls" and (4) the five‐week CarePRO‐VS program. Result: By week five, 60% of caregivers used mindful breathing 3 or more times a day. In comparison to week one, only 18.8% of caregivers used mindful breathing 3 or more times a day. As an example of a frequent user, coach call notes showed that one participant in particular self‐reported use of the relaxing techniques every week with an average of 3‐4 times a day. Mindful breathing helped her destress, stay positive, and focus on the present moment. Body scans helped her bring awareness to how she felt during stressful situations involving her father, the care recipient. She also extended the use of mindful breathing to situations beyond caregiving. At five weeks, she used mindful breathing with her father to ease his anxiety. Conclusion: These Latina caregivers implemented a new strategy that shows promising results and future research can expand on aspects of mindfulness as an equitable and accessible strategy to increase relaxation for caregivers and care recipients. To date, there are few published studies incorporating mindfulness techniques that also included Latino caregivers of people with ADRD in the U.S. [ABSTRACT FROM AUTHOR]

Background and Objectives: In this study, tortillas with improved in vitro nutritional and antihypertensive properties were developed using flours produced from nixtamalized maize (NixM) and extruded chickpea (ExtCP). The aims were (1) to find the optimal extrusion conditions to produce optimized ExtCP flour with high values of antioxidant activity (AoxA), total phenolic compounds (TPC), and in vitro protein digestibility (IVPD), and (2) to evaluate the addition effect of 30% of optimized ExtCP flour over the nutritional, technological, sensory y nutraceutical properties of tortillas prepared from commercial NixM flour. A rotatable composite central experimental design with two factors (extrusion temperature [ET] = 50°C–170°C; screw speed (SS) = 50–240 rpm) and five levels was used to optimize the extrusion process. Findings: The best combination of variables of the extrusion process to produce ExtCP flour was: ET = 143°C/SS = 138 rpm. The tortillas added with ExtCP flour had: proteins = 13.27%, total dietary fiber = 13.40%, protein chemical score = 85.42%, IVPD = 82.01%, calculated protein efficiency ratio (C‐PER) = 1.84, AoxA = 8031 µmol TE/100 g, and sensory acceptability = 8.51 (value located between I like it very much and I like it extremely). Conclusions: The tortillas made from nixtamalized maize and ExtCP flours have better in vitro nutritional and antihypertensive properties than tortillas prepared from only nixtamalized maize flour. Significance and Novelty: The addition of optimized ExtCP flour to commercial NixM flour allows obtaining functional tortillas with improved and sensory acceptable in vitro nutritional and antihypertensive properties. [ABSTRACT FROM AUTHOR]

Only PABYV was detected in 2021 and 2022, while PABYV and CABYV were found in mixed infections in all samples from 2023. Keywords: PABYV; polerovirus EN PABYV polerovirus 1 3 3 09/28/23 20230701 NES 230701 In 2021, fifty-two watermelon ( I Citrullus lanatus) i samples exhibiting yellowing virus-like symptoms (Figures 1-2) were collected from thirteen open-field plots in Murcia (southeastern Spain). All the watermelon samples collected in 2021, and a further 68 symptomatic samples collected during the 2022 and 2023 seasons, were tested for PABYV by dot-blot molecular hybridization, as described by De Moya-Ruiz I et al. i ([1]). [Extracted from the article]

Arthropod biomass is a key element in ecosystem functionality and a basic food item for many species. It must be estimated through traditional costly field sampling, normally at just a few sampling points. Arthropod biomass and plant productivity should be narrowly related because a large majority of arthropods are herbivorous, and others depend on these. Quantifying plant productivity with satellite or aerial vehicle imagery is an easy and fast procedure already tested and implemented in agriculture and field ecology. However, the capability of satellite or aerial vehicle imagery for quantifying arthropod biomass and its relationship with plant productivity has been scarcely addressed. Here, we used unmanned aerial vehicle (UAV) and satellite Sentinel‐2 (S2) imagery to establish a relationship between plant productivity and arthropod biomass estimated through ground‐truth field sampling in shrub steppes. We UAV‐sampled seven plots of 47.6–72.3 ha at a 4‐cm pixel resolution, subsequently downscaling spatial resolution to 50 cm resolution. In parallel, we used S2 imagery from the same and other dates and locations at 10‐m spatial resolution. We related several vegetation indices (VIs) with arthropod biomass (epigeous, coprophagous, and four functional consumer groups: predatory, detritivore, phytophagous, and diverse) estimated at 41–48 sampling stations for UAV flying plots and in 67–79 sampling stations for S2. VIs derived from UAV were consistently and positively related to all arthropod biomass groups. Three out of seven and six out of seven S2‐derived VIs were positively related to epigeous and coprophagous arthropod biomass, respectively. The blue normalized difference VI (BNDVI) and enhanced normalized difference VI (ENDVI) showed consistent and positive relationships with arthropod biomass, regardless of the arthropod group or spatial resolution. Our results showed that UAV and S2‐VI imagery data may be viable and cost‐efficient alternatives for quantifying arthropod biomass at large scales in shrub steppes. The relationship between VI and arthropod biomass is probably habitat‐dependent, so future research should address this relationship and include several habitats to validate VIs as proxies of arthropod biomass. [ABSTRACT FROM AUTHOR]

Bermudagrass [Cynodon dactylon (L.) Pers.] is one of the most widely cultivated turfgrass species throughout the world. It has several important attributes, such as heat and drought tolerance, and one big disadvantage, which is susceptibility to cold temperatures. Although many seeded bermudagrass cultivars are widely used in Europe, research is warranted on new varieties released in recent decades. Two identical field studies were conducted in Valencia, Spain (39° N lat) and Legnaro, Italy (45° N lat) to evaluate the turfgrass quality, winter dormancy, and spring green‐up of two new bermudagrass releases in Europe ('Arden 15' and 'MBG 002') and three older bermudagrasses ('Blackjack', 'Common', and 'Paul 1'). Even though bermudagrasses were successfully cultivated in the cooler temperature zone (45° N lat), cultivars exhibited poorer establishment and longer winter dormancy as a consequence of the lower temperatures compared with those grown in the warmer temperature zone (39° N lat). Cultivars Arden 15 and MBG 002 were able to mitigate the effects of low temperature that affected the older cultivars, especially during spring green‐up, which is an essential characteristic when growing bermudagrass in the upper limit of the transition zone. Core ideas: Bermudagrasses are distributed throughout a wide range of latitudes.At both latitudes, bermudagrasses enter dormancy with different durations.Bermudagrass dormancy lasted 4 mo at 45° N lat and 1 mo at 39° N lat.Bermudagrass spring green‐up was found quicker at 45° N lat than at 39° N lat. [ABSTRACT FROM AUTHOR]

Tumour heterogeneity is one of the main characteristics of cancer and can be categorised into inter‐ or intratumour heterogeneity. This heterogeneity has been revealed as one of the key causes of treatment failure and relapse. Precision oncology is an emerging field that seeks to design tailored treatments for each cancer patient according to epidemiological, clinical and omics data. This discipline relies on bioinformatics tools designed to compute scores to prioritise available drugs, with the aim of helping clinicians in treatment selection. In this review, we describe the current approaches for therapy selection depending on which type of tumour heterogeneity is being targeted and the available next‐generation sequencing data. We cover intertumour heterogeneity studies and individual treatment selection using genomics variants, expression data or multi‐omics strategies. We also describe intratumour dissection through clonal inference and single‐cell transcriptomics, in each case providing bioinformatics tools for tailored treatment selection. Finally, we discuss how these therapy selection workflows could be integrated into the clinical practice. [ABSTRACT FROM AUTHOR]

Loss of habitats and native species, introduction of invasive species, and changing climate regimes lead to the homogenization of landscapes and communities, affecting the availability of habitats and resources for economically important guilds, such as pollinators. Understanding how pollinators and their interactions vary along resource diversity gradients at different scales may help to determine their adaptability to the current diversity loss related to global change. We used data on 20 plant–pollinator communities along gradients of flower richness (local diversity) and landscape heterogeneity (landscape diversity) to understand how the diversity of resources at local and landscape scales affected (1) wild pollinator abundance and richness (accounting also for honey bee abundance), (2) the structure of plant–pollinator networks, (3) the proportion of actively selected interactions (those not occurring by neutral processes), and (4) pollinator diet breadth and species' specialization in networks. Wild pollinator abundance was higher overall in flower‐rich and heterogeneous habitats, while wild pollinator richness increased with flower richness (more strongly for beetles and wild bees) and decreased with honeybee abundance. Network specialization (H2′), modularity, and functional complementarity were all positively related to floral richness and landscape heterogeneity, indicating niche segregation as the diversity of resources increases at both scales. Flower richness also increased the proportion of actively selected interactions (especially for wild bees and flies), whereas landscape heterogeneity had a weak negative effect on this variable. Overall, network‐level metrics responded to larger landscape scales than pollinator‐level metrics did. Higher floral richness resulted in a wider taxonomic and functional diet for all the study guilds, while functional diet increased mainly for beetles. Despite this, specialization in networks (d′) increased with flower richness for all the study guilds, because pollinator species fed on a narrower subset of plants as communities became richer in species. Our study indicates that pollinators are able to adapt their diet to resource changes at local and landscape scales. However, resource homogenization might lead to poor and generalist pollinator communities, where functionally specialized interactions are lost. This study highlights the importance of including different scales to understand the effects of global change on pollination service through changes in resource diversity. [ABSTRACT FROM AUTHOR]

Introduction: The theoretical framework of the Alzheimer's disease continuum considers transition between stages in a unidirectional manner. Here we examine the rate of reversion from mild cognitive impairment (MCI) to normal cognition (NC) and explore a set of potential variables associated with this phenomenon. Methods: A total of 985 Spanish community‐dwelling individuals aged 70 years and over at baseline were monitored for 5 years. During this time, 173 MCI and 36 dementia cases were identified. Multi‐state Markov models were performed to characterize transitions between states through the dementia continuum. Results: The rate of reversion from MCI to NC was 11%. There were significant non‐modifiable (age, socioeconomic status, or apolipoprotein E) and modifiable factors (cognitive training or absence of affective symptoms) associated with reversion. Discussion: Overall, our results highlight that the likelihood of progression from MCI to dementia is very similar to that of reversion from MCI to NC. [ABSTRACT FROM AUTHOR]

Background and objectives: Most of the snacks in the market contain a single cereal and show nutritional deficiencies. The aim of the study was to optimize the conditions of the extrusion process for a snack with barley/corn mix and their physicochemical evaluation, amino acid content, protein digestibility, and resistant starch as a healthy snack. Findings: The regression model indicated that the variables water absorption index, water solubility index, and hardness can be explained by the models. Expansion index showed no significant effect. The optimal conditions of the process of extrusion were feed moisture 38%, die temperature 130°C, and barley/corn mix 50:50. An unflavored snack with 392.11 kcal/100 g was obtained, considering it is flavored, its estimated energy contribution is around of 446.11 kcal/100 g. The concentration of essential amino acids in the extrudate meets the requirements established by FAO/WHO/UNU for children and adolescents. Protein digestibility increased and the content of available and resistant starch was reduced. Conclusions: The optimal conditions of extrusion allowed to obtain an alternative snack with the essential amino acid requirements and higher protein digestibility. Significance and novelty: The combination of two cereals allows to supplement the requirement of essential amino acids and greater protein digestibility. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most aggressive and common glioma subtype, with a median survival of 15 months after diagnosis. Current treatments have limited therapeutic efficacy; thus, more effective approaches are needed. The glioblastoma tumoural mass is characterised by a small cellular subpopulation - glioblastoma stem cells (GSCs) - that has been held responsible for glioblastoma initiation, cell invasion, proliferation, relapse and resistance to chemo- and radiotherapy. Targeted therapies against GSCs are crucial, as is understanding the molecular mechanisms that govern the GSCs. Transforming growth factor β (TGFβ) signalling and reactive oxygen species (ROS) production are known to govern and regulate cancer stem cell biology. Among the differentially expressed genes regulated by TGFβ in a transcriptomic analysis of two different patient-derived GSCs, we found NADPH oxidase 4 (NOX4) as one of the top upregulated genes. Interestingly, when patient tissues were analysed, NOX4 expression was found to be higher in GSCs versus differentiated cells. A functional analysis of the role of NOX4 downstream of TGFβ in several patient-derived GSCs showed that TGFβ does indeed induce NOX4 expression and increases ROS production in a NOX4-dependent manner. NOX4 downstream of TGFβ regulates GSC proliferation, and NOX4 expression is necessary for TGFβ-induced expression of stem cell markers and of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), which in turn controls the cell's antioxidant and metabolic responses. Interestingly, overexpression of NOX4 recapitulates the effects induced by TGFβ in GSCs: enhanced proliferation, stemness and NRF2 expression. In conclusion, this work functionally establishes NOX4 as a key mediator of GSC biology. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a very common life-threatening malignancy. Transcription factor-like 5 (TCFL5) has been suggested to be involved in CRC. Here, we describe the expression of four alternative transcripts of TCFL5 and their relevance in CRC. Complete deletion of all isoforms drastically decreased pro-tumoural properties such as spheroids formation and in vivo tumour growth, although increased migration in CRC cell lines. Overexpression of the two main isoforms, TCFL5&lowbar;E8 and CHA, had opposite effects: TCFL5&lowbar;E8 reduced proliferation and spheroids formation, while CHA increased them. TCFL5&lowbar;E8 reduced in vivo tumour formation, while CHA had no effect. In addition, TCFL5&lowbar;E8 and CHA have different roles in the regulation of the pluripotency-related genes SOX2 and KLF4. Both isoforms bind directly to their promoters; however, TCFL5&lowbar;E8 induced SOX2 and reduced KLF4 mRNA levels, whereas CHA did the opposite. Together, our results show that TCFL5 plays an important role in the development of CRC, being however isoform-specific. This work also points to the need to analyse separately TCFL5 isoforms in cancer, due to their different and opposite functions. [ABSTRACT FROM AUTHOR]

Positive feedbacks driving habitat‐forming species recovery and population growth are often lost as ecosystems degrade. For such systems, identifying mechanisms that limit the re‐establishment of critical positive feedbacks is key to facilitating recovery. Theory predicts the primary drivers limiting system recovery shift from biological to physical as abiotic stress increases, but recent work has demonstrated that this seldom happens. We combined field and laboratory experiments to identify variation in limitations to coral recovery along an environmental stress gradient at Ningaloo Reef and Exmouth Gulf in northwest Australia. Many reefs in the region are coral depauperate due to recent cyclones and thermal stress. In general, recovery trajectories are prolonged due to limited coral recruitment. Consistent with theory, clearer water reefs under low thermal stress appear limited by biological interactions: competition with turf algae caused high mortality of newly settled corals and upright macroalgal stands drove mortality in transplanted juvenile corals. Laboratory experiments showed a positive relationship between crustose coralline algae cover and coral settlement, but only in the absence of sedimentation. Contrary to expectation, coral recovery does not appear limited by the survival or growth of recruits on turbid reefs under higher thermal stress, but to exceptionally low larval supply. Laboratory experiments showed that larval survival and settlement are unaffected by seawater quality across the study region. Rather, connectivity models predicted that many of the more turbid reefs in the Gulf are predominantly self seeded, receiving limited supply under degraded reef states. Overall, we find that the influence of oceanography can overwhelm the influences of physical and biological interactions on recovery potential at locations where environmental stressors are high, whereas populations in relatively benign physical conditions are predominantly structured by local ecological drivers. Such context‐dependent information can help guide expectations and assist managers in optimizing strategies for spatial conservation planning for system recovery. [ABSTRACT FROM AUTHOR]

Objective: To assess the test-retest reliability of the 10-step stair ascent test, Timed Up and Go (TUG) test, and 10-meter walking test under dual-task conditions in patients with fibromyalgia.Design: Test-retest reliability.Settings: Local fibromyalgia association and university facilities.Participants: Thirty-eight women with fibromyalgia.Interventions: Not applicable.Main Outcome Measures: Fear of falling and the number of falls in the last year were measured using a visual analogue scale. The 10-step stair ascent test, TUG test, and 10-meter walking test were conducted under single- and dual-task conditions. The order between single- and dual-task condition was randomized in both test and retest. Retest measurement was assessed the week following the test.Results: The reliability of the performance on the 10-step stair ascent test under dual and single conditions ranged between good (>0.75 to < 0.9) and excellent (≥0.9), but there were significant differences between test and retest. The reliability of the TUG is between good (≥0.75 to < 0.9) and excellent (≥0.9) under the dual-task condition as well as moderate (≥0.5 to <0.75) and excellent (≥0.9) under the single-task condition. The reliability of the 10-meter walking dual-task test is between moderate (≥0.5 to <0.75) and good (≥0.75 to < 0.9) under dual- and single-task condition, respectively.Conclusions: The TUG and 10-meter walking tests are reliable for assessing mobility under the dual-task condition in women with fibromyalgia. The performance on the TUG, 10-step stair ascent, and 10-meter walking test under single- and dual-task conditions was significantly related to fear of falling. These results may help healthcare professionals and researchers to interpret the effect of interventions in women with fibromyalgia. [ABSTRACT FROM AUTHOR]

Tropical hydroclimate is modulated by the position and intensity of the Intertropical Convergence Zone (ITCZ). Reconstructions and simulations of the Last Millennium (LM) suggest latitudinal variations of the ITCZ that impact the hydroclimate over large regions of the world. These ITCZ shifts have been generally linked to external radiative forcing, but analyses of the Community Earth System Model – Last Millennium Ensemble (CESM‐LME) demonstrate a significant contribution of internal variability over multidecadal and centennial timescales. In contrast to changes driven by external forcing, which are associated with an asymmetric warming between the Northern and Southern Hemispheres, the contribution of internal variability in the CESM‐LME is associated with cooling and warming of the eastern Pacific. While external forcing remains the main driver of ITCZ changes in the Atlantic basin, the contribution of internal variability in the CESM‐LME exceeds that of the forcing for the Pacific and Indian Ocean basins. Plain Language Summary: The Intertropical Convergence Zone (ITCZ) is a wide region of increased precipitation around the Equator. The position of the ITCZ changes over time. It moves to the north during summer in the Northern Hemisphere and to the south during boreal winter. In addition to these seasonal shifts, the ITCZ also changes over longer timescales. We have used a climate model to analyze ITCZ shifts over the Last Millennium. We have found that changes in the positioning of the ITCZ over the Atlantic Ocean are mainly linked to variations in solar luminosity and volcanic events, while for the Pacific and Indian Ocean, internally driven fluctuations in atmosphere and ocean states are dominant. The understanding of the mechanisms behind ITCZ shifts allows for a better assessment of tropical hydroclimatic events, such as persistent droughts and floods that are associated with alterations in the intensity and duration of tropical monsoons, as well as for better understanding its responses under intensified climate change conditions. Key Points: Last Millennium simulations contain Intertropical Convergence Zone shifts in all tropical ocean basinsIntertropical Convergence Zone shifts in the Atlantic basin are mainly linked to changes in external radiative forcingInternal variability is the dominant driver of ITCZ shifts in the Pacific and Indian Ocean basins [ABSTRACT FROM AUTHOR]

Background: Dementia has become a healthcare priority. As no disease‐modifying treatment is available, treatment is aimed to act through prevention. Frailty have been defined as a geriatric multidimensional syndrome. Being a treatable condition, interest has raised to describe the relationship between Dementia and Frailty. This study describes frailty in the Autosomal Dominant Alzheimer Disease, through the largest ADAD known group. Method: A total of 75 participants (14 with MCI and 61 with Dementia) were included in this cross sectional study. They underwent a complete assessment that included a standardized clinical examination, neuropsychological evaluation and functional scales. Frailty was assessed through the Short Physical Performance Battery (SPPB) and the Time up and Go Test (TUG). Multivariate analyses was conducted to evaluate which variables were associated with being frail in presenile onset of ADAD. Result: In the 75 patients who underwent the study, median age was of 49 years old with a cognitive profile of 18.67 % individuals with MCI, 21 % with Mild, 28 % with Moderate and 25 % Severe Dementia. According to the frailty phenotype: 60 % were non‐frail and 40 % frail. When analyzing, SPPB and TUG components: Median Gait Speed in MCI and mild dementia groups were statistically significantly lower than moderate and severe dementia (p< 0.005) and significantly greater TUG was found in moderate and severe dementia groups when compared with MCI and mild dementia(p<0.005) Both, clinical severity grouped in moderate – severe dementia (OR 6.85; CI 2.07‐22.65 p< 0.000) and hypertension (OR 5.80; CI1.56‐21.49 <0.002) are significantly associated with being frail. Conclusion: This study is the first description of frailty syndrome in ADAD with a presenile onset. The prevalence found in this population is similar than in previous reports in older adults and thus reasserts the adaptability of frailty evaluation in young patients with special clinical conditions. Our data supports the existing relationship between frailty and dementia. As the cause of dementia in our patients is purely genetic, effects of aging are controlled and excluded. This enrich science and lights up the search of new mechanisms linking both conditions. [ABSTRACT FROM AUTHOR]

Objectives: Undergraduate dentistry students in their final year often lack the knowledge and confidence required to prescribe oral health medications. Online courses could help to solve this problem through augmenting traditional teaching methods. This study assessed the effectiveness of a non-curricular, online, clinical case-based dental pharmacology course designed to improve medication management in senior dentistry students.Materials and Methods: This study developed and implemented an online dental pharmacotherapy course for 287 dentistry students in Mexico. Pre- and post-course tests evaluated knowledge acquisition, and a 5-point Likert scale questionnaire was administered to 238 participants to evaluate the course's content and educational strategies.Results: Mean knowledge scores significantly increased from pre- (5.5 ± 1.6) to post-test (9.1 ± 1.3, P < 0.001). Participants reported a high satisfaction level (70.2%) with the course content and materials, educational techniques, and instructors.Conclusion: These findings support the use of online, clinically based dental pharmacotherapy courses, in conjunction with traditional teaching methods, as a viable strategy for effectively educating dentistry students. [ABSTRACT FROM AUTHOR]

Background: Although there are studies that have examined brain functional reorganization following upper-limb amputation, understanding of the brain changes that occur in people with lower-limb amputation is limited.Objective: To investigate modifications in the brain following lower-limb amputation.Methods: We included case-control studies that evaluate neuroplasticity in the central nervous system using neuroimaging techniques. A literature search was conducted using MEDLINE, CINAHL, Web of Science, Scopus, and Cochrane.Results: Eleven articles were included (total n = 204 people with unilateral lower-limb amputation). These studies showed an increase in cerebellar gray matter volume in prosthesis users, as well as a decrease in thickness of the premotor cortex, orbitofrontal cortex, temporo-occipital junction, precentral gyrus, visual areas, and somatosensory cortex. Regarding white matter, the trials observed a decrease in the integrity at the corona radiata, the connections between the premotor areas, the fronto-occipital fasciculus and the corpus callosum. In addition, a decreased functional connectivity between cortical and subcortical areas has been described.Conclusions: Lower-limb amputation causes changes in several brain structures that may occur in the absence of pain and regardless of prosthesis use. The modifications observed include thinning or loss of gray matter volume, decrease in the integrity of the white matter connections between brain structures and changes in the functional connectivity between cortical and subcortical areas.Level Of Evidence: I. [ABSTRACT FROM AUTHOR]

Background: Recently, a relationship was found between periodontitis and chronic migraine. Calcitonin gene-related peptide (CGRP) is a key element in migraine pathophysiology. However, no information exists of the potential association between periodontal inflammation and CGRP in chronic migraine. The aim of the study was, therefore, to investigate whether there is a link between periodontitis and peripheral levels of CGRP in a cohort of patients with chronic migraine.Methods: We included 102 chronic migraineurs and 77 age- and sex-matched individuals free of headache/migraine. Full-mouth periodontal parameters were recorded and the periodontal inflamed surface area (PISA) was calculated to quantify the periodontal inflammatory status for each participant. Sociodemographic data and comorbidities were assessed by means of a standard questionnaire. We collected blood samples and serum concentrations were done for CGRP, interleukin (IL)-6 and IL-10.Results: In the chronic migraine group, patients with periodontitis had greater levels of serum CGRP (19.7 ± 6.5 versus 15.3 ± 6.2 pg/mL, P < 0.0001) and IL-6 (15.1 ± 9.2 versus 9.6 ± 6.3 pg/mL, P < 0.0001) while non-significant differences were observed with IL-10 (2.0 ± 1.0 versus 2.8 ± 1.5 pg/mL, P = 0.675) concentrations than those without periodontitis. PISA was independently associated with CGRP in patients with chronic migraine (β = 0.003; 95% confidence interval: 0.001 to 0.006, P = 0.031). PISA correlated positively with CGRP (r = 0.236; P = 0.017) and IL-6 (r = 0.262; P = 0.008) in chronic migraine.Conclusions: Periodontal inflammation is associated with increased circulating levels of CGRP in chronic migraineurs. Elucidating the exact mechanisms through which periodontitis and CGRP are linked in these patients deserves further investigation. [ABSTRACT FROM AUTHOR]

Transcranial random noise stimulation (tRNS) increases performance in some perceptual tasks. However, little is known about its effect on creativity. Although dorsolateral prefrontal cortex (DLPFC) has been postulated as an important cortical area related to creativity, the relative role of left and right DLPFC is still unclear. We aimed to compare the effect of anodal left/cathodal right (L + R−) and cathodal left/anodal right (L − R+) tRNS over the DLPFC. Eighty‐four participants were randomly assigned to L + R−, L−R+ or sham group. Current was set at 2 mA (100–500 Hz) with a 1 mA direct current offset (20 min). Creativity was assessed before and during tRNS with the Remotes Associates Test (RAT), Unusual Uses (UU) and Picture Completion (PC) from Torrance Test of Creative Thinking, nine‐dot problem and matchstick arithmetic problems. Bootstrapped analysis of covariance (under‐stimulation scores controlling for baseline) showed that L + R− and L − R+ groups had higher scores than sham in UU whereas only L + R− improved in RAT compared to sham. The L − R+ group performed significantly better than L + R− and sham groups in PC, nine‐dot problem and matchstick arithmetic problems. L + R− DLPFC may help verbal creative thinking whereas the L − R + seems to produce a "releasing effect" through insight problem solving and originality. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common cause of dementia. Although it presents a long preclinical period, treatment has yet to be found, and individuals at risk, like first‐degree relatives, are being studied to identify early detection markers to maximise the effectiveness of treatments. Functional connectivity changes have been observed even at this early stage (Ramirez‐Toraño et al., 2021), but most disregard its temporal dimension. This study investigates the value of a simple estimation of dynamic functional connectivity (dFC) in a longitudinal follow‐up of individuals with varying risk of the disease, as this parameter is expected to decrease across the disease continuum (Grieder et al, 2018). Method: 95 cognitively unimpaired participants with a family history of AD (FH+) and 39 without it (FH‐) underwent two longitudinal 5‐minute resting‐state magnetoencephalography recordings, approximately 3 years apart. FC in the low alpha band (8‐10 Hz) was estimated in 4‐second segments using phase locking value in the source space, and the standard deviation (STD) across epochs was calculated. Then, a STD ratio was derived dividing the STD values of the follow‐up session by those of the baseline session, and then averaged over nodes belonging to the same regions of the automatic anatomical labelling atlas. Left‐tailed t‐tests between the STD ratio of both groups in each ROI link (n_comparisons = 3160) were calculated and corrected for multiple comparisons with a false discovery rate using q = 0.20. Result: 13 links show a significantly lower dFC in the FH+ group than in the FH‐ group (Figure 1). Interestingly, these links involve regions where amyloid‐beta deposits early in the AD continuum (Mattsson et al., 2019), and are strongly related to the default mode network (Palmqvist et al. 2017). Conclusion: This study suggests that a simple estimation of dFC like STD may be useful in early detection pathological patterns characteristic of AD, even in cognitively unimpaired individuals at risk. The fact that dFC decreases were detected in areas where amyloid deposits appear at an early stage might indicate that these changes are related to changes in the excitation/inhibition ratio, which will be further studied in upcoming investigations. [ABSTRACT FROM AUTHOR]

Background: Machine learning (ML) algorithms are generating great interest for early diagnose of Alzheimer's disease (AD). Despite several approaches have been developed, limited research has been conducted on the impact of feature selection in classification performance. In this study we compare two feature selection methods, LASSO and Elastic Nets (EN), applied to ML algorithms based on magnetoencephalography (MEG) data from mild cognitive impairment (MCI) patients. Method: An eyes‐closed resting‐state MEG recording was performed by 262 participants (117 healthy controls and 145 MCI). Functional connectivity measures were estimated for all classical frequency bands using the Phase‐Locking Value. To develop the ML algorithms, specific regions of interest from the default mode network, based on the Automatic Anatomical Labelling atlas, were selected, resulting in a total of 325 features. After dividing the dataset into training (80%) and test (20%) sets, feature selection with 10000 iterations and five‐fold cross validation was performed independently for each band using LASSO and EN algorithms. Afterwards, several classification models were trained with a five‐fold cross validation and then validated on the test set, over 500 iterations. Result: The classifier showing the best performance was the linear Support Vector Machine for the beta frequency band (12‐30 Hz). Given the similarity of the training and test performance values, the results reveal that overfitting was avoided when using the 45 features selected by LASSO instead of the 47 features selected by EN, reaching a validation accuracy of 77%. Additionally, LASSO consistently identified three functional connectivity links as relevant in all frequency bands but alpha: right superior frontal gyrus & right superior frontal gyrus orbital, left posterior cingulate cortex & left hippocampus, right posterior cingulate cortex & right precuneus. Conclusion: ML algorithms applied to MEG data can successfully discriminate MCI patients from healthy controls. In addition, LASSO algorithm applied for feature selection leads to better classification performance. Moreover, the resulting relevant functional connectivity links involve areas affected by AD pathology even in early stages of its development (López‐Sanz et al., 2019). Further exploration of this methodology is needed, combining this data with structural neuroimaging or complementary biomarkers. [ABSTRACT FROM AUTHOR]

Background: Optical Coherence Tomography angiography (OCT‐A) is a novel tool that allows the detection of retinal vascular changes. The comparison of OCT‐A measures with brain vascular burden is essential to validate the former as a surrogate of cerebrovascular damage and biomarker of cognitive decline. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus assessed by OCT‐A with measures of cerebrovascular pathology quantified by brain magnetic resonance imaging (MRI) in a cohort of non‐demented individuals. Method: Clinical, demographical, APOE ε4 status, amyloid status, OCT‐A and brain MRI data from non‐demented participants of the FACEHBI and BIOFACE studies were included. We analyzed the association of macular VD in four quadrants (superior, nasal, inferior and temporal) with brain vascular burden using the Fazekas scale scores (dichotomized in two categories, 0‐1 vs 2‐3), assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) quantified by Freesurfer assessed in a multiple regression analysis. We additionally explored the associations of macular VD with hippocampal volume, ventricles volume and Alzheimer Disease cortical signature (ADCS) thickness assessed in a multiple regression analysis. All analyses were adjusted for age and dyslipidemia. Result: The study cohort comprised 188 participants: 89 with subjective cognitive decline (SCD) and 99 with mild cognitive impairment (MCI). Logistic regression analysis showed no significant differences of regional macular VD between the two Fazekas groups (all, p>0.05). Multiple regression analysis showed no significant association of regional macular VD with the volume of WMH (all, p>0.05). Macular VD in the nasal and inferior quadrants were positively associated with hippocampal volume (p = 0.009 and p = 0.021, respectively), but no association was detected with ventricles volume or ADCS thickness (both p>0.05). Conclusion: Our study showed that retinal vascular measures (regional macular VD in the superficial vascular plexus) assessed by OCT‐A were not associated with brain vascular damage quantified by the Fazekas scale and the WMH burden n in a cohort of non‐demented research participants with SCD and MCI. [ABSTRACT FROM AUTHOR]

Background: in the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p‐tau‐mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre‐screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma exosomes (pEXOs) are gaining popularity as a new source of biomarkers for the early stages of AD development Method: to identify an exosome proteomics signature linked to prodromal AD, we performed a cross‐sectional study on two groups of patients with early‐onset MCI (EOMCI) (Aβ +/‐) in which 184 biomarkers were measured in pEXOs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink© proteomics. Result: the obtained results showed that proteins measured in pEXOs from EOMCI patients with established amyloidosis correlated with CSF p‐tau181 levels, brain ventricle volume changes, white matter hyperintensities, and MMSE scores. In addition, the correlations of pEXOs proteins with different parameters were able to discriminate between EOMCI Aβ(+) and Aβ(‐) patients, whereas the CSF or plasma proteome did not. Conclusion: our findings suggest that pEXOs could be able to provide information regarding the initial amyloidotic changes of AD. At this early stage, our results may indicate that pEXOs biomarker profile is associated with the AD‐specific neurodegeneration process governed by p‐tau and Aβ. Circulating exosomes may acquire a pathological protein signature of AD before raw plasma, becoming potential biomarkers for identifying subjects at the earliest stages of AD development. However, additional research is required to comprehend the molecular pathways underlying these findings and validate the obtained results in an independent cohort. [ABSTRACT FROM AUTHOR]

Despite impressive and durable responses, nonsmall cell lung cancer (NSCLC) patients treated with anaplastic lymphoma kinase (ALK) inhibitors (ALK‐Is) ultimately progress due to development of resistance. Here, we have evaluated the clinical utility of circulating tumor DNA (ctDNA) profiling by next‐generation sequencing (NGS) upon disease progression. We collected 26 plasma and two cerebrospinal fluid samples from 24 advanced ALK‐positive NSCLC patients at disease progression to an ALK‐I. These samples were analyzed by NGS and digital PCR. A tool to retrieve variants at the ALK locus was developed (VALK tool). We identified at least one resistance mutation in the ALK locus in ten (38.5%) plasma samples; the G1269A and G1202R mutations were the most prevalent among patients progressing to first‐ and second‐generation ALK‐Is, respectively. Overall, 61 somatic mutations were detected in 14 genes: TP53, ALK, PIK3CA, SMAD4, MAP2K1(MEK1), FGFR2, FGFR3, BRAF, EGFR, IDH2, MYC, MET, CCND3, and CCND1. Specifically, a deletion in exon 19 in EGFR, a non‐V600 BRAF mutation (G466V), and the F129L mutation in MAP2K1 were identified in four patients who showed no objective survival benefit from ALK‐Is. Potential ALK‐I‐resistance mutations were also found in PIK3CA and IDH2. Finally, a c‐MYC gain, along with a loss of CCND1 and FGFR3, was detected in a patient progressing on a first‐line treatment with crizotinib. We conclude that NGS analysis of liquid biopsies upon disease progression identified different putative ALK‐I‐resistance mutations in most cases and could be a valuable approach for therapy decision making. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the effect of suturing on the early wound healing of donor sites of subepithelial connective tissue grafts (SCTG), harvested by the single incision technique (SIT), following the application of a collagen sponge.Methods: Thirty-six patients were randomized to receive a collagen sponge with or without sutures in the palatal donor sites following connective tissue grafting via the SIT. Outcome variables were early healing index (EHI) at 7, 14, and 30 days, self-reported pain using a visual analogue scale (VAS) recorded on the 0 to 100 scale at 7 and 14 days, and immediate and delayed bleeding.Results: No significant differences were found between groups at baseline. EHI index showed no differences between groups in all-time intervals. Eight subjects from suture group (SG) and 10 from no suture group (nSG) showed complete wound closure at day 14 (P >0.05) and at 30 days, complete closure was observed in 35 out of 36 patients. Four subjects from the SG and three from the nSG had immediate bleeding (P >0.05), while delayed bleeding was observed in two subjects from the SG and three from the nSG during the first week of healing (P >0.05). No differences were found in VAS scale between groups (SG, 36.2 ± 24.8; nSG, 21.5 ± 24.2, P >0.05).Conclusion: It can be concluded that when a collagen sponge is placed in palatal donor areas of SCTG harvest by means of the SIT (incision length of ≈15 mm), sutured and non-sutured sites display similar early wound healing outcomes and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Background and objectives: The production of precooked rice has mainly been applied to long rice varieties, while japonica varieties are significantly less represented, especially Spanish varieties. The aim of this paper was to model the water mass flow process in precooked round‐shaped rice (Bahía‐Senia) for the soaking (Peleg model) and drying phases (drying by hot air and by combined hot air and microwaves, Fick, Midili, and Page models). Optical and mechanical properties after drying were recorded. Cooking tests were also performed. Findings: The results show that optimum soaking process was achieved at 35°C during 20 min. For the drying stage, water loss increases using microwave energy at 2.45 GHz and no variations with air temperature were registered. Thus, the optimal drying conditions were achieved at 40°C combined with microwave during 42 min. Conclusions: Precooked round rice processing conditions have been established. This treatment would reduce the final cooking time (96 ºC) for the user by 94%, which implies that in only 3 min, the precooked rice would reach the same level of moisture as the control rice after 20 min of cooking. Significance and novelty: These findings can be used by food industry in selecting the proper soaking and drying conditions that favors the production of precooked round‐shaped rice. [ABSTRACT FROM AUTHOR]

Intraspecific plant diversity can significantly impact insect herbivore populations in natural systems. Yet, its role as an insect pest control strategy in agriculture has received less attention, and little is known about which crop traits are important to herbivores in different landscape contexts. Moreover, empirical economic analyses on the cost‐effectiveness of varietal mixtures are lacking. We used varietal mixtures of Brassica oleracea crops on working farms to examine how two metrics of intraspecific crop diversity, varietal richness and number of plant colors (color richness), affect crop damage and the incidence and abundance of two insect pest species: Pieris rapae and Phyllotreta spp. We evaluated the context‐dependency of varietal mixtures by sampling early‐ and late‐season plantings of B. oleracea crops in farms across a gradient of landscape composition. We developed crop budgets and used a net present value analysis to assess the impact of varietal mixtures on input and labor costs, crop revenues, and profit. We found context‐dependent effects of varietal mixtures on both pests. In early‐season plantings, color richness did not affect Phyllotreta spp. populations. However, increasing varietal richness reduced Phyllotreta spp. incidence in simple landscapes dominated by cropland, but this trend was reversed in complex landscapes dominated by natural habitats. In late‐season plantings, color richness reduced the incidence and abundance of P. rapae larvae, but only in complex landscapes where their populations were highest. Varietal richness had the same effect on P. rapae larvae as color richness. Unexpectedly, we consistently found lower pest pressure and reduced crop damage in simple landscapes. Although varietal mixtures did not affect crop damage, increasing color richness corresponded with increased profits, due to increased revenue and a marginal reduction in labor and input costs. We demonstrate varietal mixtures can significantly impact pest populations, and this effect can be mediated by intraspecific variation in crop color. However, the strength and direction of these effects vary by season, landscape composition, and pest species. The association between varietal color richness and profitability indicates farmers could design mixtures to enhance economic returns. We recommend additional research on the benefits of intraspecific trait variation for farmers. [ABSTRACT FROM AUTHOR]

Malignant melanoma (MM) is the most aggressive and life‐threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient‐derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem‐like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by high‐resolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum‐derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC‐derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic‐based study aimed at characterizing exosomes derived from melanoma CSCs and patients' serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC‐derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common cancers, still characterized by high mortality rates. As lipid metabolism contributes to cancer metabolic reprogramming, several lipid metabolism genes are considered prognostic biomarkers of cancer. Statins are a class of lipid‐lowering compounds used in treatment of cardiovascular disease that are currently studied for their antitumor effects. However, their exact mechanism of action and specific conditions in which they should be administered remains unclear. Here, we found that simvastatin treatment effectively promoted antiproliferative effects and modulated lipid metabolism‐related pathways in non‐small cell lung cancer (NSCLC) cells and that the antiproliferative effects of statins were potentiated by overexpression of acyl‐CoA synthetase long‐chain family member 3 (ACSL3). Moreover, ACSL3 overexpression was associated with worse clinical outcome in patients with high‐grade NSCLC. Finally, we found that patients with high expression levels of ACSL3 displayed a clinical benefit of statins treatment. Therefore, our study highlights ACSL3 as a prognostic biomarker for NSCLC, useful to select patients who would obtain a clinical benefit from statin administration. [ABSTRACT FROM AUTHOR]

Gallbladder stones (cholecystolithiasis) are the main risk factor for gallbladder cancer (GBC), a lethal biliary malignancy with poor survival rates worldwide. Gallbladder stones are thought to damage the gallbladder epithelium and trigger chronic inflammation. Preneoplastic lesions that arise in such an inflammatory microenvironment can eventually develop into invasive carcinoma, through mechanisms that are not fully understood. Here, we developed a novel gallbladder preneoplasia mouse model through the administration of two lithogenic diets (a low‐ or a high‐cholesterol diet) in wild‐type C57BL/6 mice over a period of 9 months. Additionally, we evaluated the chemopreventive potentials of the anti‐inflammatory drug aspirin and the cholesterol absorption inhibitor ezetimibe. Both lithogenic diets induced early formation of gallbladder stones, together with extensive inflammatory changes and widespread induction of metaplasia, an epithelial adaptation to tissue injury. Dysplastic lesions were presented only in mice fed with high‐cholesterol diet (62.5%) in late stages (9th month), and no invasive carcinoma was observed at any stage. The cholesterol absorption inhibitor ezetimibe inhibited gallbladder stone formation and completely prevented the onset of metaplasia and dysplasia in both lithogenic diets, whereas aspirin partially reduced metaplasia development only in the low‐cholesterol diet setting. This model recapitulates several of the structural and inflammatory findings observed in human cholecystolithiasic gallbladders, making it relevant for the study of gallbladder carcinogenesis. In addition, our results suggest that the use of cholesterol absorption inhibitors and anti‐inflammatory drugs can be evaluated as chemopreventive strategies to reduce the burden of GBC among high‐risk populations. [ABSTRACT FROM AUTHOR]

The crosstalk between cancer cells and the tumor microenvironment has been implicated in cancer progression and metastasis. Fibroblasts and immune cells are widely known to be attracted to and modified by cancer cells. However, the role of pericytes in the tumor microenvironment beyond endothelium stabilization is poorly understood. Here, we report that pericytes promoted colorectal cancer (CRC) cell proliferation, migration, invasion, stemness, and chemoresistance in vitro, as well as tumor growth in a xenograft CRC model. We demonstrate that coculture with human CRC cells induced broad transcriptomic changes in pericytes, mostly associated with TGF‐β receptor activation. The prognostic value of a TGF‐β response signature in pericytes was analyzed in CRC patient data sets. This signature was found to be a good predictor of CRC relapse. Moreover, in response to stimulation by CRC cells, pericytes expressed high levels of TGF‐β1, initiating an autocrine activation loop. Investigation of secreted mediators and underlying molecular mechanisms revealed that IGFBP‐3 is a key paracrine factor from activated pericytes affecting CRC cell migration and invasion. In summary, we demonstrate that the interplay between pericytes and CRC cells triggers a vicious cycle that stimulates pericyte cytokine secretion, in turn increasing CRC cell tumorigenic properties. Overall, we provide another example of how cancer cells can manipulate the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Objective: To determine the most frequently used outcome measures in total knee replacement rehabilitation trials.Literature Survey: Systematic review of randomized trials searched in five databases: Web of Science, MEDical Literature Analysis and Retrieval System, Physiotherapy Evidence Database, Scopus, and Cochrane Library.Methodology: Trials were included if participants underwent total knee replacement rehabilitation and outcome measures were used to assess rehabilitation outcomes. A descriptive synthesis determined the frequency of using outcome measures and preferred assessment time points. Outcomes were classified into eight categories: patient- and clinician-reported function, performance-based function, balance, anxiety and depressive symptoms, quality of life, and others.Synthesis: Eighty-one trials were included and 102 different outcome measures were classified. The most frequently reported outcome was knee range of motion, used in 54% of trials, followed by a visual analog scale of pain (43%) and Western Ontario and McMaster Universities Arthritis Index (WOMAC; 40%). Patient- and clinician-reported function were the categories most frequently assessed (74%), whereas performance-based measures were implemented by 56% of trials. The most frequent assessment time points were 1 week presurgery (52%) and 3 months postsurgery (39%).Conclusions: There is consensus regarding the need to evaluate functional outcomes in total knee replacement rehabilitation trials but none regarding the outcome measure that should be used. These findings suggest that most trials include patient- and clinician-reported functional measures, along with pain and performance-based measures in trial designs. [ABSTRACT FROM AUTHOR]

Background and objectives: The aim of this study was to develop a wall material using rice starch (Oryza sativa) to optimize the microencapsulation of vanilla extract by spray drying. Native starch rice was hydrolyzed, succinated, extruded, and characterized. Findings: The peak viscosity of modified starches was reduced from 3,875 cP to <100 cP by effect of the modification step. Native starch was gelatinized by extrusion according to gelatinization enthalpy (∆H J/g). Natural vanilla extract was encapsulated, and the most optimal conditions for the drying process were air inlet temperature of 125°C, 14.0% of total solids, and 86.2% of encapsulation efficiency. The scanning electron microscopy evidenced the formation of microcapsules; however, the confocal laser scanning microscopy showed no interaction between the wall material and the vanilla extract. This could be related to the zeta potential values of the vanilla extract and the wall material. Conclusions: Modified rice starch is a potential wall material for the encapsulation of different bioactive compounds in the food sector. Significance and novelty: Chemical and physical modifications such as hydrolysis, succinylation, and extrusion in native rice starch offer adequate properties to achieve 86.2% encapsulation efficiency of natural vanilla extract using spray drying. [ABSTRACT FROM AUTHOR]

The high biodiversity of the Mexican montane forests is concentrated on the Trans‐Mexican Volcanic Belt, where several Protected Natural Areas exist. Our study examines the projected changes in suitable climatic habitat for five conifer species that dominate these forests. The species are distributed sequentially in overlapping altitudinal bands: Pinus hartwegii at the upper timberline, followed by Abies religiosa, the overwintering host of the Monarch butterfly at the Monarch Butterfly Biosphere Reserve, P. pseudostrobus, the most important in economic terms, and P. devoniana and P. oocarpa, which are important for resin production and occupy low altitudes where montane conifers merge with tropical dry forests. We fit a bioclimatic model to presence–absence observations for each species using the Random Forests classification tree with ground plot data. The models are driven by normal climatic variables from 1961 to 1990, which represents the reference period for climate‐induced vegetation changes. Climate data from an ensemble of 17 general circulation models were run through the classification tree to project current distributions under climates described by the RCP 6.0 watts/m2 scenario for the decades centered on years 2030, 2060 and 2090. The results suggest that, by 2060, the climate niche of each species will occur at elevations that are between 300 to 500 m higher than at present. By 2060, habitat loss could amount to 46–77%, mostly affecting the lower limits of distribution. The two species at the highest elevation, P. hartwegii and A. religiosa, would suffer the greatest losses while, at the lower elevations, P. oocarpa would gain the most niche space. Our results suggest that conifers will require human assistance to migrate altitudinally upward in order to recouple populations with the climates to which they are adapted. Traditional in situ conservation measures are likely to be equivalent to inaction and will therefore be incapable of maintaining current forest compositions. [ABSTRACT FROM AUTHOR]

Challenges in the collection of vouchers, either because of the physical properties of the material (species difficult to collect or to press, e.g., palms, cycads, toxic plants, and cacti) or because drying may have a negative effect on taxonomic characters (e.g., colour), recommend the use of photographs to complement herbarium specimens. In a series of cases (enumerated in the present contribution), however, it may be impossible to collect material and, thus, photographs may be the only option to document the presence of a plant in a given locality. We propose in this paper some guidelines for the standardization of photographs intended for deposit in herbaria. [ABSTRACT FROM AUTHOR]

Tibouchina (Melastomataceae: Melastomateae) is an exclusively Neotropical genus that currently includes close to 310 species. These were first described or assigned to 16 other genera, a reflection of the complex taxonomic and phylogenetic history of the genus. Previous phylogenetic analyses have shown that the genus is polyphyletic. Here we present an expanded analysis that includes representatives of 28 genera of New World Melastomateae, as well as representatives of Old World Melastomateae and members of the Marcetieae and Microlicieae. Over 300 species were sequenced for nrITS and the plastid spacers accD‐psaI and psbK‐psbL. We recovered a large clade of Neotropical Melastomateae that contains Tibouchina along with at least 13 other Neotropical genera. Moreover, Tibouchina is not recovered as monophyletic because three mostly Central American and five mostly Andean genera are nested within it, albeit each these genera are recovered as monophyletic. Many of the previously recognized sections of Tibouchina are recovered as monophyletic or paraphyletic providing a basis for a new classification. Tibouchina is here re‐circumscribed into four genera that are each monophyletic and easily diagnosable. This results in a narrowly circumscribed Tibouchina and the re‐establishment of Pleroma and Chaetogastra, and the description of a new genus, Andesanthus. Pleroma now also includes Itatiaia, Microlepis and Svitramia. Brachyotum is maintained until its relationship to Chaetogastra can be further examined. This new taxonomic arrangement is more informative and convenient than merging eight other genera into Tibouchina. An identification key, descriptions of genera, and lists of taxa with their current generic assignment and necessary nomenclatural novelties are also presented here. [ABSTRACT FROM AUTHOR]

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome‐wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta‐analyzed with additional genome‐wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta‐analysis strategy revealed the ANKRD31‐rs4704171 and NDUFAF6‐rs10098778 and confirmed SCIMP‐rs7225151 and CD33‐rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta‐analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series. Highlights: We detected three gene categories operating differently in AD subgroups of patients.Vasculature regulation may be an essential part of the causative mechanism in pure AD.Two novel signals reached genome‐wide significance in ANKRD31 and NDUFAF6loci.We confirmed SCIMP‐rs7225151 and CD33‐rs3865444 to be genome‐wide significant.Genetic discoveries are strongly impacted by the presence of subgroups of AD. [ABSTRACT FROM AUTHOR]

Background: Swimming has no effect on bone mass or structure. Therefore, adolescent swimmers present similar bone strength values when compared to normo-active controls, and lower values when compared to weight-bearing athletes. It thus seems necessary to try to improve bone structure and strength of adolescent swimmers through a weight-bearing intervention in order to reduce the risk of suffering osteoporosis later in life.Objective: To evaluate the effects of a 6-month whole body vibration (WBV) intervention on bone strength and structure of adolescent swimmers.Design: Randomized controlled trial.Setting: Research center.Participants: A total of 51 swimmers (14.4 ± 2.0 years) participated in the study.Methods: Swimmers were randomly allocated into 2 groups: 20 swimmers (9 females) who only performed their swimming training, and 31 swimmers (15 females) who performed their swimming training and received a WBV intervention (3.6-11.6 g) 3 times per week during 6 months (VIB).Outcome Measurements: Peripheral quantitative computed tomography was performed in the nondominant tibia of all swimmers at 4%, 38%, and 66% of the tibia length before and after the intervention.Results: No differences between groups in any bone structure variable were found at pre- or postintervention. Both groups presented similar improvements in time, and no group by time interactions were found, suggesting that the WBV intervention was not intense enough to achieve positive changes in bone strength or structure.Conclusion: WBV, at the chosen intensities and durations, had no effect on adolescent swimmers' bone strength or structure. Future studies should test other weight-bearing interventions aiming to improve bone strength and structure of adolescent swimmers.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]