FMN2 Makes Perinuclear Actin to Protect Nuclei during Confined Migration and Promote Metastasis.

Cell migration in confined 3D tissue microenvironments is critical for both normal physiological functions and dissemination of tumor cells. We discovered a cytoskeletal structure that prevents damage to the nucleus during migration in confined microenvironments. The formin-family actin filament nucleator FMN2 associates with and generates a perinuclear actin/focal adhesion (FA) system that is distinct from previously characterized actin/FA structures. This system controls nuclear shape and positioning in cells migrating on 2D surfaces. In confined 3D microenvironments, FMN2 promotes cell survival by limiting nuclear envelope damage and DNA double-strand breaks. We found that FMN2 is upregulated in human melanomas and showed that disruption of FMN2 in mouse melanoma cells inhibits their extravasation and metastasis to the lung. Our results indicate a critical role for FMN2 in generating a perinuclear actin/FA system that protects the nucleus and DNA from damage to promote cell survival during confined migration and thus promote cancer metastasis.

A Functional Role for Antibodies in Tuberculosis.

While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcγRIII, and distinct Ab glycosylation patterns. Moreover, compared to Abs from Atb, Abs from Ltb drove enhanced phagolysosomal maturation, inflammasome activation, and, most importantly, macrophage killing of intracellular Mtb. Combined, these data point to a potential role for Fc-mediated Ab effector functions, tuned via differential glycosylation, in Mtb control.

Phosphatidylserine vesicles enable efficient en bloc transmission of enteroviruses.

A central paradigm within virology is that each viral particle largely behaves as an independent infectious unit. Here, we demonstrate that clusters of enteroviral particles are packaged within phosphatidylserine (PS) lipid-enriched vesicles that are non-lytically released from cells and provide greater infection efficiency than free single viral particles. We show that vesicular PS lipids are co-factors to the relevant enterovirus receptors in mediating subsequent infectivity and transmission, in particular to primary human macrophages. We demonstrate that clustered packaging of viral particles within vesicles enables multiple viral RNA genomes to be collectively transferred into single cells. This study reveals a novel mode of viral transmission, where enteroviral genomes are transmitted from cell-to-cell en bloc in membrane-bound PS vesicles instead of as single independent genomes. This has implications for facilitating genetic cooperativity among viral quasispecies as well as enhancing viral replication.

Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion.

Immune exclusion predicts poor patient outcomes in multiple malignancies, including triple-negative breast cancer (TNBC)1. The extracellular matrix (ECM) contributes to immune exclusion2. However, strategies to reduce ECM abundance are largely ineffective or generate undesired outcomes3,4. Here we show that discoidin domain receptor 1 (DDR1), a collagen receptor with tyrosine kinase activity5, instigates immune exclusion by promoting collagen fibre alignment. Ablation of Ddr1 in tumours promotes the intratumoral penetration of T cells and obliterates tumour growth in mouse models of TNBC. Supporting this finding, in human TNBC the expression of DDR1 negatively correlates with the intratumoral abundance of anti-tumour T cells. The DDR1 extracellular domain (DDR1-ECD), but not its intracellular kinase domain, is required for immune exclusion. Membrane-untethered DDR1-ECD is sufficient to rescue the growth of Ddr1-knockout tumours in immunocompetent hosts. Mechanistically, the binding of DDR1-ECD to collagen enforces aligned collagen fibres and obstructs immune infiltration. ECD-neutralizing antibodies disrupt collagen fibre alignment, mitigate immune exclusion and inhibit tumour growth in immunocompetent hosts. Together, our findings identify a mechanism for immune exclusion and suggest an immunotherapeutic target for increasing immune accessibility through reconfiguration of the tumour ECM.

Long-term declines in chlorophyll a and variable phenology revealed by a 60-year estuarine plankton time series.

Long-term ecological time series provide a unique perspective on the emergent properties of ecosystems. In aquatic systems, phytoplankton form the base of the food web and their biomass, measured as the concentration of the photosynthetic pigment chlorophyll a (chl a), is an indicator of ecosystem quality. We analyzed temporal trends in chl a from the Long-Term Plankton Time Series in Narragansett Bay, Rhode Island, USA, a temperate estuary experiencing long-term warming and changing anthropogenic nutrient inputs. Dynamic linear models were used to impute and model environmental variables (1959 to 2019) and chl a concentrations (1968 to 2019). A long-term chl a decrease was observed with an average decline in the cumulative annual chl a concentration of 49% and a marked decline of 57% in winter-spring bloom magnitude. The long-term decline in chl a concentration was directly and indirectly associated with multiple environmental factors that are impacted by climate change (e.g., warming temperatures, water column stratification, reduced nutrient concentrations) indicating the importance of accounting for regional climate change effects in ecosystem-based management. Analysis of seasonal phenology revealed that the winter-spring bloom occurred earlier, at a rate of 4.9 ± 2.8 d decade-1. Finally, the high degree of temporal variation in phytoplankton biomass observed in Narragansett Bay appears common among estuaries, coasts, and open oceans. The commonality among these marine ecosystems highlights the need to maintain a robust set of phytoplankton time series in the coming decades to improve signal-to-noise ratios and identify trends in these highly variable environments.

The maize preligule band is subdivided into distinct domains with contrasting cellular properties prior to ligule outgrowth.

The maize ligule is an epidermis-derived structure that arises from the preligule band (PLB) at a boundary between the blade and sheath. A hinge-like auricle also develops immediately distal to the ligule and contributes to blade angle. Here, we characterize the stages of PLB and early ligule development in terms of topography, cell area, division orientation, cell wall rigidity and auxin response dynamics. Differential thickening of epidermal cells and localized periclinal divisions contributed to the formation of a ridge within the PLB, which ultimately produces the ligule fringe. Patterns in cell wall rigidity were consistent with the subdivision of the PLB into two regions along a distinct line positioned at the nascent ridge. The proximal region produces the ligule, while the distal region contributes to one epidermal face of the auricles. Although the auxin transporter PIN1 accumulated in the PLB, observed differential auxin transcriptional response did not underlie the partitioning of the PLB. Our data demonstrate that two zones with contrasting cellular properties, the preligule and preauricle, are specified within the ligular region before ligule outgrowth.

StARD9 is a novel lysosomal kinesin required for membrane tubulation, cholesterol transport and Purkinje cell survival.

The pathological accumulation of cholesterol is a signature feature of Niemann-Pick type C (NPC) disease, in which excessive lipid levels induce Purkinje cell death in the cerebellum. NPC1 encodes a lysosomal cholesterol-binding protein, and mutations in NPC1 drive cholesterol accumulation in late endosomes and lysosomes (LE/Ls). However, the fundamental role of NPC proteins in LE/L cholesterol transport remains unclear. Here, we demonstrate that NPC1 mutations impair the projection of cholesterol-containing membrane tubules from the surface of LE/Ls. A proteomic survey of purified LE/Ls identified StARD9 as a novel lysosomal kinesin responsible for LE/L tubulation. StARD9 contains an N-terminal kinesin domain, a C-terminal StART domain, and a dileucine signal shared with other lysosome-associated membrane proteins. Depletion of StARD9 disrupts LE/L tubulation, paralyzes bidirectional LE/L motility and induces accumulation of cholesterol in LE/Ls. Finally, a novel StARD9 knock-out mouse recapitulates the progressive loss of Purkinje cells in the cerebellum. Together, these studies identify StARD9 as a microtubule motor protein responsible for LE/L tubulation and provide support for a novel model of LE/L cholesterol transport that becomes impaired in NPC disease.

Aging and neurodegeneration: From molecular mechanisms to therapeutic interventions.

Protein aggregation is a common age-associated process and can be a pathological hallmark of various neurodegenerative conditions, possibly because of an age-associated decline in the activity of components of the proteostasis network. The specific molecular drivers of protein aggregation in certain cell types are not well understood, posing tremendous challenges to current research aimed at devising strategies to treat neurodegenerative diseases. This preface introduces the special issue "Aging and Neurodegeneration: from molecular mechanisms to therapeutic interventions," featuring articles that assess the drivers of pathology in the aging cell, including oxidative stress, protein glycation/aggregation, and mitochondrial impairment.

Altered hippocampal doublecortin expression in Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by motor and non-motor symptoms. Motor symptoms include bradykinesia, resting tremors, muscular rigidity, and postural instability, while non-motor symptoms include cognitive impairments, mood disturbances, sleep disturbances, autonomic dysfunction, and sensory abnormalities. Some of these symptoms may be influenced by the proper hippocampus functioning, including adult neurogenesis. Doublecortin (DCX) is a microtubule-associated protein that plays a pivotal role in the development and differentiation of migrating neurons. This study utilized postmortem human brain tissue of PD and age-matched control individuals to investigate DCX expression in the context of adult hippocampal neurogenesis. Our findings demonstrate a significant reduction in the number of DCX-expressing cells within the subgranular zone (SGZ), as well as a decrease in the nuclear area of these DCX-positive cells in postmortem brain tissue obtained from PD cases, suggesting an impairment in the adult hippocampal neurogenesis. Additionally, we found that the nuclear area of DCX-positive cells correlates with pH levels. In summary, we provide evidence supporting that the process of hippocampal adult neurogenesis is likely to be compromised in PD patients before cognitive dysfunction, shedding light on potential mechanisms contributing to the neuropsychiatric symptoms observed in affected individuals. Understanding these mechanisms may offer novel insights into the pathophysiology of PD and possible therapeutic avenues.

A perspective on the metastasis suppressor field.

Metastasis is the leading cause of cancer patient mortality. Metastasis suppressors are genes that, upon reexpression in metastatic tumor cells to levels observed in their nonmetastatic counterparts, significantly reduce metastasis without affecting the growth of the primary tumor. Analysis of > 30 metastasis suppressors revealed complex mechanisms of action that include multiple signaling pathways, transcriptional patterns, posttranscriptional regulatory mechanisms, and potential contributions of genomic stability. Clinical testing of strategies to re-establish a validated metastasis suppressor pathway in tumors is best directed to the adjuvant setting, with the goal of inhibiting the outgrowth of occult micrometastases.

Is our understanding of aquatic ecosystems sufficient to quantify ecologically driven climate feedbacks?

The Earth functions as an integrated system-its current habitability to complex life is an emergent property dependent on interactions among biological, chemical, and physical components. As global warming affects ecosystem structure and function, so too will the biosphere affect climate by altering atmospheric gas composition and planetary albedo. Constraining these ecosystem-climate feedbacks is essential to accurately predict future change and develop mitigation strategies; however, the interplay among ecosystem processes complicates the assessment of their impact. Here, we explore the state-of-knowledge on how ecological and biological processes (e.g., competition, trophic interactions, metabolism, and adaptation) affect the directionality and magnitude of feedbacks between ecosystems and climate, using illustrative examples from the aquatic sphere. We argue that, despite ample evidence for the likely significance of many, our present understanding of the combinatorial effects of ecosystem dynamics precludes the robust quantification of most ecologically driven climate feedbacks. Constraining these effects must be prioritized within the ecological sciences for only by studying the biosphere as both subject and arbiter of global climate can we develop a sufficiently holistic view of the Earth system to accurately predict Earth's future and unravel its past.

La Terre fonctionne comme un système intégré­son habitabilité pour une vie complexe est une propriété émergente qui dépend des interactions entre les composantes biologiques, chimiques et physiques. Le réchauffement climatique affecte la structure et la fonction des écosystèmes, et en retour, la biosphère affecte également le climat en modifiant la composition des gaz atmosphériques et l'albédo planétaire. Il est essentiel de quantifier ces rétroactions entre les écosystèmes et le climat afin de prédire avec précision les changements futurs et élaborer des stratégies d'atténuation; cependant, l'interaction entre les processus écologiques complique l'évaluation de leurs impacts. Dans cet article, nous examinons l'état des connaissances sur la façon dont les processus écologiques et biologiques (par exemple, la concurrence, les interactions trophiques, le métabolisme, l'adaptation) affectent la directionnalité et l'ampleur des rétroactions entre les écosystèmes et le climat à l'aide d'exemples issus du monde aquatique. Nous soutenons que, malgré les nombreuses preuves de l'importance de plusieurs de ces rétroactions, notre compréhension limitée des effets additifs des processus écosystémiques empêche de faire une quantification robuste de la plupart des rétroactions climatiques d'origine écologique. Circonscrire ces effets doit être une priorité pour les sciences aquatiques, car ce n'est qu'en étudiant la biosphère en tant que sujet et arbitre du climat planétaire que nous pourrons développer une vision suffisamment holistique du système terrestre pour prédire avec précision l'avenir de la Terre et élucider son passé.

ANKRD1 expression is aberrantly upregulated in the mdm mouse model of muscular dystrophy and induced by stretch through NFκB.

The muscular dystrophy with myositis (mdm) mouse model results in a severe muscular dystrophy due to an 83-amino-acid deletion in the N2A region of titin, an expanded sarcomeric protein that functions as a molecular spring which senses and modulates the response to mechanical forces in cardiac and skeletal muscles. ANKRD1 is one of the muscle ankyrin repeat domain proteins (MARPs) a family of titin-associated, stress-response molecules and putative transducers of stretch-induced signaling in skeletal muscle. The aberrant over-activation of Nuclear factor Kappa B (NF-κB) and the Ankyrin-repeat domain containing protein 1 (ANKRD1) occurs in several models of progressive muscle disease including Duchenne muscular dystrophy. We hypothesized that mechanical regulation of ANKRD1 is mediated by NF-κB activation in skeletal muscles and that this mechanism is perturbed by small deletion of the stretch-sensing titin N2A region in the mdm mouse. We applied static mechanical stretch of the mdm mouse diaphragm and cyclic mechanical stretch of C2C12 myotubes to examine the interaction between NF-κΒ and ANKRD1 expression utilizing Western blot and qRTPCR. As seen in skeletal muscles of other severe muscular dystrophies, an aberrant increased basal expression of NF-κB and ANKRD1 were observed in the diaphragm muscles of the mdm mice. Our data show that in the mdm diaphragm, basal levels of NF-κB are increased, and pharmacological inhibition of NF-κB does not alter basal levels of ANKRD1. Alternatively, NF-κB inhibition did alter stretch-induced ANKRD1 upregulation. These data show that NF-κB activity is at least partially responsible for the stretch-induced expression of ANKRD1.

Natural habitat connectivity and organic management modulate pest dispersal, gene flow, and natural enemy communities.

The simplification and fragmentation of agricultural landscapes generate effects on insects at multiple spatial scales. As each functional group perceives and uses the habitat differently, the response of pest insects and their associated natural enemies to environmental changes varies. Therefore, landscape structure may have consequences on gene flow among pest populations in space. This study aimed to evaluate the effects of local and landscape factors, at multiple scales, on the local infestation, gene flow and broad dispersion dynamics of the pest insect Bemisia tabaci (Genn.) Middle East-Asia Minor 1 (MEAM-1, former biotype B) (Hemiptera: Aleyrodidae) and its associated natural enemies in a tropical agroecosystem. We evaluated the abundance of B. tabaci populations and their natural enemy community in 20 tomato farms in Brazil and the gene flow between farms from 2019 to 2021. Landscapes dominated by agriculture resulted in larger B. tabaci populations and higher gene flow, especially in conventional farms. A higher density of native vegetation patches disfavored pest populations, regardless of the management system. The results revealed that whitefly responds to intermediate spatial scales and that landscape factors interact with management systems to modulate whitefly populations on focal farms. Conversely, whitefly natural enemies benefited from higher amounts of natural vegetation at small spatial scales, while the connectivity between natural habitat patches was beneficial for natural enemies regardless of the distance from the focal farm. The resulting dispersion model predicts that the movement of whiteflies between farms increases as the amount of natural vegetation decreases. Our findings demonstrate that landscape features, notably landscape configuration, can mediate infestation episodes, as they affect pest insects and natural enemies in opposite ways. We also showed that landscape features interact with farm traits, which highlights the need for management strategies at multiple spatial scales. In conclusion, we demonstrated the importance of the conservation of natural areas as a key strategy for area-wide ecological pest management and the relevance of organic farming to benefit natural enemy communities in tropical agroecosystems.

Assessing supervisor versus trainee viewpoints of entrustment through cognitive and affective lenses: an artificial intelligence investigation of bias in feedback.

The entrustment framework redirects assessment from considering only trainees' competence to decision-making about their readiness to perform clinical tasks independently. Since trainees and supervisors both contribute to entrustment decisions, we examined the cognitive and affective factors that underly their negotiation of trust, and whether trainee demographic characteristics may bias them. Using a document analysis approach, we adapted large language models (LLMs) to examine feedback dialogs (N = 24,187, each with an associated entrustment rating) between medical student trainees and their clinical supervisors. We compared how trainees and supervisors differentially documented feedback dialogs about similar tasks by identifying qualitative themes and quantitatively assessing their correlation with entrustment ratings. Supervisors' themes predominantly reflected skills related to patient presentations, while trainees' themes were broader-including clinical performance and personal qualities. To examine affect, we trained an LLM to measure feedback sentiment. On average, trainees used more negative language (5.3% lower probability of positive sentiment, p < 0.05) compared to supervisors, while documenting higher entrustment ratings (+ 0.08 on a 1-4 scale, p < 0.05). We also found biases tied to demographic characteristics: trainees' documentation reflected more positive sentiment in the case of male trainees (+ 1.3%, p < 0.05) and of trainees underrepresented in medicine (UIM) (+ 1.3%, p < 0.05). Entrustment ratings did not appear to reflect these biases, neither when documented by trainee nor supervisor. As such, bias appeared to influence the emotive language trainees used to document entrustment more than the degree of entrustment they experienced. Mitigating these biases is nonetheless important because they may affect trainees' assimilation into their roles and formation of trusting relationships.

Exploring access cavity through non-carious cervical lesions: Impacts on instrumentation, obturation, and fracture resistance in mandibular incisors.

AIM: To compare the effects of Cervical Access Cavity (CervAC) and Traditional Access Cavity (TradAC) on root canal preparation, root canal filling, and fracture resistance in mandibular incisors. METHODOLOGY: Twenty recently extracted and intact mandibular incisors were initially scanned using a micro-CT device. The specimens were anatomically matched to create two groups (n = 10). A wedge-shaped non-carious cervical lesion (NCCL) was created on the buccal aspect of all teeth using a double-faced segmented diamond disc. In group 1, a TradAC was prepared, whilst in group 2, access was created through the simulated NCCL using a round diamond bur 1012. After root canal preparation with Rotate instruments sizes 15/0.04, 20/0.04, and 25/0.04, the teeth were scanned again and evaluated for root canal volume and surface area, static voxels, volume of removed dental tissue, and dentine thickness. After that, the root canals were filled using the single-cone technique, teeth were restored with composite resin, and subsequently rescanned to calculate the volume of filling materials and voids. Then, the restored teeth were subjected to fracture resistance tests using a universal testing machine. Statistical comparisons between groups were performed with the Mann-Whitney test or the Student's t-test, with a statistical significance level of 5%. RESULTS: Statistical comparisons indicated no significant differences between groups in terms of root canal volume, surface area, static voxels, removed root dentine, root canal filling volume, percentage of voids, or fracture resistance load (p > .05). Conversely, teeth prepared with TradAC showed a significantly higher percentage of dental tissue removed from the crown (p = .001) and a greater volume of filling material remnants in the pulp chamber (p < .001) compared to the CervAC group. A significantly lower percentage reduction in dentine thickness was observed only on the mesial aspect of root at Level 1 in TradAC group (p = .008). CONCLUSIONS: CervAC can be considered a viable alternative approach in the presence of NCCL in mandibular incisors.

Metarhizium pingshaense photolyase expression and virulence to Rhipicephalus microplus after UV-B exposure.

The current study examined the impact of ultraviolet (UV)-B radiation in Metarhizium pingshaense blastospores' photolyase expression and their virulence against Rhipicephalus microplus. Blastospores were exposed to UV under laboratory and field conditions. Ticks were treated topically with fungal suspension and exposed to UV-B in the laboratory for three consecutive days. The expression of cyclobutane pyrimidine dimmers (CPDs)-photolyase gene maphr1-2 in blastospores after UV exposure followed by white light exposure was accessed after 0, 8, 12, 24, 36, and 48 h. Average relative germination of blastospores 24 h after in vitro UV exposure was 8.4% lower than 48 h. Despite this, the relative germination of blastospores exposed to UV in the field 18 h (95.7 ± 0.3%) and 28 h (97.3 ± 0.8%) after exposure were not different (p > 0.05). Ticks treated with fungus and not exposed to UV exhibited 0% survival 10 days after the treatment, while fungus-treated ticks exposed to UV exhibited 50 ± 11.2% survival. Expression levels of maphr1-2 8, 12, and 24 h after UV-B exposure were not different from time zero. Maphr1-2 expression peak in M. pingshaense blastospores occurred 36 h after UV-B exposure, in the proposed conditions and times analyzed, suggesting repair mechanisms other than CPD-mediated-photoreactivation might be leading blastospores' germination from 0 to 24 h.

Nurse judgements of hospitalized patients' safety concerns are affected by patient, nurse and event characteristics: A factorial survey experiment.

AIM: To test the influences of patient, safety event and nurse characteristics on nurse judgements of credibility, importance and intent to report patients' safety concerns. DESIGN: Factorial survey experiment. METHODS: A total of 240 nurses were recruited and completed an online survey including demographic information and responses to eight factorial vignettes consisting of unique combinations of eight patient and event factors. Hierarchical multivariate analysis was used to test influences of vignette factors and nurse characteristics on nurse judgements. RESULTS: The intraclass coefficients for nurse judgements suggest that the variation among nurses exceeded the influence of contextual vignette factors. Several significant sources of nurse variation were identified, including race/ethnicity, suggesting a complex relationship between nurses' characteristics and their potential biases, and the influence of personal and patient factors on nurses' judgements, including the decision to report safety concerns. CONCLUSION: Nurses are key players in the system to manage patient safety concerns. Variation among nurses and how they respond to scenarios of patient safety concerns highlight the need for nurse-level intervention. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Complex factors influence nurses' judgement, interpretation and reporting of patients' safety concerns. IMPACT: Understanding nurse judgement regarding patient-expressed safety concerns is critical for designing processes and systems that promote reporting. Multiple event and patient characteristics (type of event and apparent harm, and patient gender, race/ethnicity, socioeconomic status, and communication approach) as well as participant characteristics (race/ethnicity, gender, years of experience and primary hospital area) impacted participants' judgements of credibility, degree of concern and intent to report. These findings will help guide patient safety nurse education and training. REPORTING METHOD: STROBE guidelines. PATIENT OR PUBLIC CONTRIBUTION: Members of the public, including patient advocates, were involved in content validation of the vignette scenarios, norming photographs used in the factorial survey and testing the survey functionality.

Bichectomy Surgery and EMG Masticatory Muscles Function in Adult Women: A Longitudinal Study.

AIM: This longitudinal study aimed to evaluate the electromyographic activity of the masseter and temporal muscles in adult women who underwent buccal fat removal. MATERIALS AND METHODS: The sample consisted of 20 healthy adult women with no temporomandibular dysfunction and normal occlusion, who were assessed before, 30, and 60 days after the surgery. The electromyographic signal of the masseter and temporal muscles was captured through mandibular tasks including rest, protrusion, right and left laterality, and maximum voluntary contraction with and without parafilm. The results obtained were tabulated and the Shapiro-Wilk normality test was performed, which indicated a normal distribution. Statistical analysis was performed using the repeated measures test (p < 0.05). RESULTS: Significant differences were observed between time periods in maximum voluntary contraction for the left masseter muscle (p = 0.006) and in maximum voluntary contraction with parafilm for the right temporal (p = 0.03) and left temporal (p = 0.03) muscles. CONCLUSION: Bichectomy surgery did not modify the electromyographic activity of the masseter and temporal muscles during the rest task but may have influenced variations in the electromyographic signal during different mandibular tasks after 60 days of surgery, suggesting compensatory adaptations and functional recovery. CLINICAL SIGNIFICANCE: Understanding the impact of buccal fat removal surgery on the stomatognathic system function provides insights into postoperative functional recovery and potential compensatory adaptations, guiding clinical management and rehabilitation strategies for patients undergoing such procedures. How to cite this article: Cardoso AHDLS, Palinkas M, Bettiol NB, et al. Bichectomy Surgery and EMG Masticatory Muscles Function in Adult Women: A Longitudinal Study. J Contemp Dent Pract 2024;25(3):207-212.

National Cancer Institute Collaborative Workshop on Shaping the Landscape of Brain Metastases Research: challenges and recommended priorities.

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.