Digital cognitive assessments as low-burden markers for predicting future cognitive decline and tau accumulation across the Alzheimer's spectrum.

Digital cognitive assessments, particularly those that can be done at home, present as low burden biomarkers for participants and patients alike, but their effectiveness in diagnosis of Alzheimer's or predicting its trajectory is still unclear. Here, we assessed what utility or added value these digital cognitive assessments provide for identifying those at high risk for cognitive decline. We analyzed >500 ADNI participants who underwent a brief digital cognitive assessment and Aß/tau PET scans, examining their ability to distinguish cognitive status and predict cognitive decline. Performance on the digital cognitive assessment were superior to both cortical Aß and entorhinal tau in detecting mild cognitive impairment and future cognitive decline, with mnemonic discrimination deficits emerging as the most critical measure for predicting decline and future tau accumulation. Digital assessments are effective in identifying at-risk individuals, supporting their utility as low-burden tools for early Alzheimer's detection and monitoring.

Optimised graphite/carbon black loading of recycled PLA for the production of low-cost conductive filament and its application to the detection of ß-estradiol in environmental samples.

The production, optimisation, physicochemical, and electroanalytical characterisation of a low-cost electrically conductive additive manufacturing filament made with recycled poly(lactic acid) (rPLA), castor oil, carbon black, and graphite (CB-G/PLA) is reported. Through optimising the carbon black and graphite loading, the best ratio for conductivity, low material cost, and printability was found to be 60% carbon black to 40% graphite. The maximum composition within the rPLA with 10 wt% castor oil was found to be an overall nanocarbon loading of 35 wt% which produced a price of less than £0.01 per electrode whilst still offering excellent low-temperature flexibility and reproducible printing. The additive manufactured electrodes produced from this filament offered excellent electrochemical performance, with a heterogeneous electron (charge) transfer rate constant, k0 calculated to be (2.6 ± 0.1) × 10-3 cm s-1 compared to (0.46 ± 0.03) × 10-3 cm s-1 for the commercial PLA benchmark. The additive manufactured electrodes were applied to the determination of ß-estradiol, achieving a sensitivity of 400 nA µM-1, a limit of quantification of 70 nM, and a limit of detection of 21 nM, which compared excellently to other reports in the literature. The system was then applied to the detection of ß-estradiol within four real water samples, including tap, bottled, river, and lake water, where recoveries between 95 and 109% were obtained. Due to the ability to create high-performance filament at a low material cost (£0.06 per gram) and through the use of more sustainable materials such as recycled polymers, bio-based plasticisers, and naturally occurring graphite, additive manufacturing will have a permanent place within the electroanalysis arsenal in the future.

Clinically recognized sleep disorders in people living with HIV.

OBJECTIVE: Despite recognition that people with HIV (PWH) are more vulnerable to sleep issues, there is limited understanding of clinically recognized sleep disorders in this population. Our objective was to evaluate the full spectrum of sleep disorder types diagnosed among PWH in care. METHODS: We conducted a retrospective cohort study of PWH, and a comparator group of people without HIV (PWoH), in a large healthcare system. The incidence of clinically diagnosed sleep disorders was calculated using Poisson regression for three outcomes: any type of sleep disorder, insomnia, and sleep apnea. Incidence was compared between PWH and PWoH by computing the adjusted incidence rate ratio (aIRR), accounting for sleep disorder risk factors. Comparisons to PWoH were made for all PWH combined, then with PWH stratified by HIV management status (well-managed HIV defined as being on antiretroviral therapy, HIV RNA <200 copies/mL, and CD4 count ≥500 cells/µL). RESULTS: The study included 9076 PWH and 205 178 PWoH (mean age 46 years, 90% men). Compared with PWoH, sleep disorder incidence was greater among PWH overall [aIRR = 1.19, 95% confidence interval (CI): 1.12-1.26], particularly for insomnia (aIRR = 1.56, 95% CI: 1.45-1.67). Sleep apnea incidence was lower among PWH (aIRR = 0.90, 95% CI: 0.84-0.97). In HIV management subgroups, PWH without well-managed HIV had lower sleep apnea incidence (vs. PWoH: aIRR = 0.79, 95% CI: 0.70-0.89) but PWH with well-managed HIV did not (vs. PWoH: aIRR = 0.97, 95% CI: 0.89-1.06). CONCLUSIONS: PWH have high sleep disorder incidence, and insomnia is the most common clinical diagnosis. Lower sleep apnea incidence among PWH may reflect underdiagnosis in those with sub-optimally treated HIV and will be important to investigate further.

Urinary eicosanoid levels in early life and risk of atopic disease in childhood.

INTRODUCTION: Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs) and leukotrienes (LTs) with a pathophysiological role in established atopic disease. However, their role in the inception of disease is unclear. We aimed to investigate the association between urinary eicosanoids in early life and development of atopic disease. METHODS: We quantified the levels of 21 eicosanoids in urine from children from the COPSAC2010 (age 1 year, n=450) and VDAART (age 3 years, n=575) mother-child cohorts and analyzed the associations with development of wheeze/asthma, atopic dermatitis, and biomarkers of Type-2 inflammation, applying FDR5% multiple testing correction. RESULTS: In both cohorts, analyses adjusted for environmental determinants showed that higher TXA2 eicosanoids in early life were associated with increased risk of developing atopic dermatitis (P

Quantifying the impacts of future shoreline modification on biodiversity in a case study of coastal Georgia, United States.

People often modify the shoreline to mitigate erosion and protect property from storm impacts. The 2 main approaches to modification are gray infrastructure (e.g., bulkheads and seawalls) and natural or green infrastructure (NI) (e.g., living shorelines). Gray infrastructure is still more often used for coastal protection than NI, despite having more detrimental effects on ecosystem parameters, such as biodiversity. We assessed the impact of gray infrastructure on biodiversity and whether the adoption of NI can mitigate its loss. We examined the literature to quantify the relationship of gray infrastructure and NI to biodiversity and developed a model with temporal geospatial data on ecosystem distribution and shoreline modification to project future shoreline modification for our study location, coastal Georgia (United States). We applied the literature-derived empirical relationships of infrastructure effects on biodiversity to the shoreline modification projections to predict change in biodiversity under different NI versus gray infrastructure scenarios. For our study area, which is dominated by marshes and use of gray infrastructure, when just under half of all new coastal infrastructure was to be NI, previous losses of biodiversity from gray infrastructure could be mitigated by 2100 (net change of biodiversity of +0.14%, 95% confidence interval -0.10% to +0.39%). As biodiversity continues to decline from human impacts, it is increasingly imperative to minimize negative impacts when possible. We therefore suggest policy and the permitting process be changed to promote the adoption of NI.

Cuantificación del impacto de la futura modificación de la costa sobre la biodiversidad en un estudio de caso de la costa de Georgia, Estados Unidos Resumen Las personas modifican con frecuencia la costa para mitigar la erosión o proteger su propiedad del impacto de las tormentas. Los dos enfoques principales para la modificación son la infraestructura gris (p. ej.: mamparos y malecones) y la infraestructura verde o natural (IN) (p.ej.: costas vivientes). La infraestructura gris es más común que la IN, a pesar de que tiene efectos dañinos sobre los parámetros ambientales, como la biodiversidad. Evaluamos el impacto de la infraestructura gris sobre la biodiversidad y si la adopción de la IN puede mitigar su pérdida. Analizamos la literatura para cuantificar la relación de la infraestructura gris y la IN con la biodiversidad. También desarrollamos un modelo con datos geoespaciales temporales sobre la distribución de los ecosistemas y la modificación de la costa para proyectar la modificación costera en el futuro en nuestra localidad de estudio: la costa de Georgia, Estados Unidos. Aplicamos las relaciones empíricas derivadas de la literatura de los efectos de la infraestructura sobre la biodiversidad a las proyecciones de modificación de la costa para predecir el cambio en la biodiversidad bajo diferentes escenarios de infraestructura gris versus IN. En nuestra área de estudio, que está dominada por marismas y usa infraestructura gris, cuando un poco menos de la mitad de toda la infraestructura costera nueva debería ser IN, las pérdidas previas de biodiversidad a partir de la infraestructura gris podrían mitigarse para 2100 (cambio neto de la biodiversidad de +0.14%, 95% intervalo de confianza ­0.10% a +0.39%). Conforme la biodiversidad siga en declive por el impacto humano, cada vez es más imperativo minimizar el impacto negativo cuando sea posible. Por lo tanto, sugerimos que se modifiquen las políticas y el proceso de permisos para promover la adopción de la IN.

FDA Approval Summary: Fruquintinib for the Treatment of Refractory Metastatic Colorectal Cancer.

On November 8, 2023, the FDA approved fruquintinib, an inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3, for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine­, oxaliplatin­, and irinotecan­based chemotherapy, an anti­VEGF therapy, and, if RAS wild­type and medically appropriate, an anti EGFR therapy. Approval was based on Study FRESCO-2, a globally-conducted, double-blind, placebo-controlled randomized trial. The primary endpoint was overall survival (OS). The key secondary endpoint was progression-free survival (PFS). A total of 691 patients were randomized (461 and 230 into the fruquintinib and placebo arms, respectively). Fruquintinib provided a statistically significant improvement in OS with a hazard ratio (HR) of 0.66 (95% CI: 0.55, 0.80; p<0.001). The median OS was 7.4 months (95% CI: 6.7, 8.2) in the fruquintinib arm and 4.8 months (95% CI: 4.0, 5.8) for the placebo arm. Adverse events observed were generally consistent with the known safety profile associated with inhibition of the VEGFR. The results of FRESCO-2 were supported by the FRESCO study, a double-blind, single country, placebo-controlled, randomized trial in patients with refractory mCRC who have been previously treated with fluoropyrimidine­, oxaliplatin­, and irinotecan­based chemotherapy. In FRESCO, the OS HR was 0.65 (95% CI: 0.51, 0.83; p<0.001). FDA concluded that the totality of the evidence from FRESCO-2 and FRESCO supported an indication for patients with mCRC with prior treatment with fluoropyrimidine, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild­type and medically appropriate, an anti-EGFR therapy.

Manipulating Local Chemistry and Coherent Structures for High-Rate and Long-Life Sodium-Ion Battery Cathodes.

Layered sodium transition-metal (TM) oxides generally suffer from severe capacity decay and poor rate performance during cycling, especially at a high state of charge (SoC). Herein, an insight into failure mechanisms within high-voltage layered cathodes is unveiled, while a two-in-one tactic of charge localization and coherent structures is devised to improve structural integrity and Na+ transport kinetics, elucidated by density functional theory calculations. Elevated Jahn-Teller [Mn3+O6] concentration on the particle surface during sodiation, coupled with intense interlayer repulsion and adverse oxygen instability, leads to irreversible damage to the near-surface structure, as demonstrated by X-ray absorption spectroscopy and in situ characterization techniques. It is further validated that the structural skeleton is substantially strengthened through the electronic structure modulation surrounding oxygen. Furthermore, optimized Na+ diffusion is effectively attainable via regulating intergrown structures, successfully achieved by the Zn2+ inducer. Greatly, good redox reversibility with an initial Coulombic efficiency of 92.6%, impressive rate capability (86.5 mAh g-1 with 70.4% retention at 10C), and enhanced cycling stability (71.6% retention after 300 cycles at 5C) are exhibited in the P2/O3 biphasic cathode. It is believed that a profound comprehension of layered oxides will herald fresh perspectives to develop high-voltage cathode materials for sodium-ion batteries.

Multidrug-Resistant Escherichia coli Remains Susceptible to Metal Ions and Graphene-Based Compounds.

Escherichia coli is listed as a priority 1 pathogen on the World Health Organization (WHO) priority pathogen list. For this list of pathogens, new antibiotics are urgently needed to control the emergence and spread of multidrug-resistant strains. This study assessed eighteen metal ions, graphene, and graphene oxide for their antimicrobial efficacy against E. coli in both planktonic and biofilm growth states and the potential synergy between metal ions and graphene-based compounds. Molybdenum and tin ions exhibited the greatest antimicrobial activity against the planktonic states of the isolates with minimal inhibitory concentrations (MIC) ranging between 13 mg/L and 15.6 mg/L. Graphene oxide had no antimicrobial effect against any of the isolates, while graphene showed a moderate effect against E. coli (MIC, 62.5 mg/L). Combinations of metal ions and graphene-based compounds including tin-graphene, tin-graphene oxide, gold-graphene, platinum-graphene, and platinum-graphene oxide exhibited a synergistic antimicrobial effect (FIC ≤ 0.5), inhibiting the planktonic and biofilm formation of the isolates regardless of their antibiotic-resistant profiles. The bactericidal effect of the metal ions and the synergistic effects when combined with graphene/graphene oxide against medically relevant pathogens demonstrated that the antimicrobial efficacy was increased. Hence, such agents may potentially be used in the production of novel antimicrobial/antiseptic agents.

Collaterals and stroke reperfusion: Too few leads to too much.

Adequate reperfusion after ischemic stroke is a major determinant of functional outcome yet remains unpredictable and insufficient for most survivors. In this issue of Neuron, Binder et al.1 identify leptomeningeal collaterals (LMCs) in mice and human patients as a key factor in regulating reperfusion and hemorrhagic transformation following stroke.

AI Quality Standards in Health Care: Rapid Umbrella Review.

BACKGROUND: In recent years, there has been an upwelling of artificial intelligence (AI) studies in the health care literature. During this period, there has been an increasing number of proposed standards to evaluate the quality of health care AI studies. OBJECTIVE: This rapid umbrella review examines the use of AI quality standards in a sample of health care AI systematic review articles published over a 36-month period. METHODS: We used a modified version of the Joanna Briggs Institute umbrella review method. Our rapid approach was informed by the practical guide by Tricco and colleagues for conducting rapid reviews. Our search was focused on the MEDLINE database supplemented with Google Scholar. The inclusion criteria were English-language systematic reviews regardless of review type, with mention of AI and health in the abstract, published during a 36-month period. For the synthesis, we summarized the AI quality standards used and issues noted in these reviews drawing on a set of published health care AI standards, harmonized the terms used, and offered guidance to improve the quality of future health care AI studies. RESULTS: We selected 33 review articles published between 2020 and 2022 in our synthesis. The reviews covered a wide range of objectives, topics, settings, designs, and results. Over 60 AI approaches across different domains were identified with varying levels of detail spanning different AI life cycle stages, making comparisons difficult. Health care AI quality standards were applied in only 39% (13/33) of the reviews and in 14% (25/178) of the original studies from the reviews examined, mostly to appraise their methodological or reporting quality. Only a handful mentioned the transparency, explainability, trustworthiness, ethics, and privacy aspects. A total of 23 AI quality standard-related issues were identified in the reviews. There was a recognized need to standardize the planning, conduct, and reporting of health care AI studies and address their broader societal, ethical, and regulatory implications. CONCLUSIONS: Despite the growing number of AI standards to assess the quality of health care AI studies, they are seldom applied in practice. With increasing desire to adopt AI in different health topics, domains, and settings, practitioners and researchers must stay abreast of and adapt to the evolving landscape of health care AI quality standards and apply these standards to improve the quality of their AI studies.

SERPINE1: Role in Cholangiocarcinoma Progression and a Therapeutic Target in the Desmoplastic Microenvironment.

A heterogenous population of inflammatory elements, other immune and nonimmune cells and cancer-associated fibroblasts (CAFs) are evident in solid malignancies where they coexist with the growing tumor mass. In highly desmoplastic malignancies, CAFs are the prominent mesenchymal cell type in the tumor microenvironment (TME), where their presence and abundance signal a poor prognosis. CAFs play a major role in the progression of various cancers by remodeling the supporting stroma into a dense, fibrotic matrix while secreting factors that promote the maintenance of cancer stem-like characteristics, tumor cell survival, aggressive growth and metastasis and reduced sensitivity to chemotherapeutics. Tumors with high stromal fibrotic signatures are more likely to be associated with drug resistance and eventual relapse. Identifying the molecular underpinnings for such multidirectional crosstalk among the various normal and neoplastic cell types in the TME may provide new targets and novel opportunities for therapeutic intervention. This review highlights recent concepts regarding the complexity of CAF biology in cholangiocarcinoma, a highly desmoplastic cancer. The discussion focuses on CAF heterogeneity, functionality in drug resistance, contributions to a progressively fibrotic tumor stroma, the involved signaling pathways and the participating genes.

Workshop report - interdisciplinary metabolomic epidemiology: the pathway to clinical translation.

Metabolomic epidemiology studies are complex and require a broad array of domain expertise. Although many metabolite-phenotype associations have been identified; to date, few findings have been translated to the clinic. Bridging this gap requires understanding of both the underlying biology of these associations and their potential clinical implications, necessitating an interdisciplinary team approach. To address this need in metabolomic epidemiology, a workshop was held at Metabolomics 2023 in Niagara Falls, Ontario, Canada that highlighted the domain expertise needed to effectively conduct these studies -- biochemistry, clinical science, epidemiology, and assay development for biomarker validation -- and emphasized the role of interdisciplinary teams to move findings towards clinical translation.

Cognitive modeling of the Mnemonic Similarity Task as a digital biomarker for Alzheimer's Disease.

AD related pathologies, such as beta-amyloid (Aß) and phosphorylated tau (pTau), are evident decades before any noticeable decline in memory occurs. Identifying individuals during this asymptomatic phase is crucial for timely intervention. The Mnemonic Similarity Task (MST), a modified recognition memory task, is especially relevant for early AD screening, as it assesses hippocampal integrity, a region affected (both directly and indirectly) early in the progression of the disease. Further, strong inferences on the underlying cognitive mechanisms that support performance on this task can be made using Bayesian cognitive modeling. We assessed whether analyzing MST performance using a cognitive model could detect subtle changes in cognitive function and AD biomarker status prior to overt cognitive decline. We analyzed MST data from >200 individuals (young, cognitively healthy older adults, and individuals with MCI), a subset of which also had existing CSF Aß and pTau data. Traditional performance scores and cognitive modeling using multinomial processing trees was applied to each participants MST data using Bayesian approaches. We assessed how well each could predict age group, memory ability, MCI status, Aß/pTau status using ROC analyses. Both approaches predicted age group membership equally, but cognitive modeling approaches exceeded traditional metrics in all other comparisons. This work establishes that cognitive modeling of the MST can detect individuals with AD prior to cognitive decline, making it a potentially useful tool for both screening and monitoring older adults during the asymptomatic phase of AD.

Discovery of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has been responsible for numerous large-scale outbreaks in the last twenty years. Currently, there are no FDA-approved therapeutics for any alphavirus infection. CHIKV non-structural protein 2 (nsP2), which contains a cysteine protease domain, is essential for viral replication, making it an attractive target for a drug discovery campaign. Here, we optimized a CHIKV nsP2 protease (nsP2pro) biochemical assay for the screening of a 6,120-compound cysteine-directed covalent fragment library. Using a 50% inhibition threshold, we identified 153 hits (2.5% hit rate). In dose-response follow up, RA-0002034, a covalent fragment that contains a vinyl sulfone warhead, inhibited CHIKV nsP2pro with an IC 50 of 58 ± 17 nM, and further analysis with time-dependent inhibition studies yielded a k inact /K I of 6.4 x 10 3 M -1 s -1 . LC-MS/MS analysis determined that RA-0002034 covalently modified the catalytic cysteine in a site-specific manner. Additionally, RA-0002034 showed no significant off-target reactivity against a panel of cysteine proteases. In addition to the potent biochemical inhibition of CHIKV nsP2pro activity and exceptional selectivity, RA-0002034 was tested in cellular models of alphavirus infection and effectively inhibited viral replication of both CHIKV and related alphaviruses. This study highlights the discovery and characterization of the chemical probe RA-0002034 as a promising hit compound from covalent fragment-based screening for development toward a CHIKV or pan-alphavirus therapeutic. Significance Statement: Chikungunya virus is one of the most prominent and widespread alphaviruses and has caused explosive outbreaks of arthritic disease. Currently, there are no FDA-approved drugs to treat disease caused by chikungunya virus or any other alphavirus-caused infection. Here, we report the discovery of a covalent small molecule inhibitor of chikungunya virus nsP2 protease activity and viral replication of four diverse alphaviruses. This finding highlights the utility of covalent fragment screening for inhibitor discovery and represents a starting point towards the development of alphavirus therapeutics targeting nsP2 protease.

Inter-rater reliability of the dynamic neuromuscular stabilization diaphragm tests among individuals with non-specific low back pain and neck pain.

BACKGROUND: The Dynamic Neuromuscular Stabilization (DNS) diaphragm test and intra-abdominal pressure regulation test (IAPRT) are qualitative clinical tests that assess postural stability provided by the diaphragm. OBJECTIVE: Evaluate the inter-rater reliability of the diaphragm test and IAPRT between an experienced and novice DNS clinician among individuals with non-specific low back pain (LBP) and neck pain. METHODS: Forty-five participants with non-specific LBP and/or neck pain were assessed by an experienced and novice DNS physiotherapist in the diaphragm test and IAPRT, and scored on a visual analog scale (VAS) according to five different criteria. RESULTS: Moderate reliability was noted when assessing LBP and neck pain patients in the diaphragm test and IAPRT (p < 0.001). Moderate reliability also existed when assessing only LBP (p < 0.001) or neck pain (p = 0.002, p = 0.009) independently. Patients with lower pain (NPRS score of 5 or < ) demonstrated lower intra-class correlation coefficients, yet still moderate reliability in the diaphragm test (p = 0.004) and IAPRT (p = 0.001). Patients with higher pain (NPRS score of 6 or > ) demonstrated greater intra-class correlation coefficients, with the diaphragm test resulting in good reliability (p < 0.001). CONCLUSIONS: The diaphragm test and IAPRT demonstrate moderate reliability between an experienced and novice DNS clinician when evaluating LBP and neck pain patients, with a greater degree of reliability noted in patients suffering from higher reported pain.

Age-Related Brain Atrophy and the Positive Effects of Behavioral Enrichment in Middle-Aged Beagles.

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of ß-amyloid (Aß) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy.

Comparing gastrointestinal stromal tumor outcomes between geriatric and non-geriatric patients: A population-based analysis.

BACKGROUND: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non-geriatric patients. METHODS: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. Variables included age, sex, surgery, cancer-specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5-year survival (5YS). Log-Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery. RESULTS: The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7-69.5). Cancer-specific death was 39.11% in 2000 & 3.33% in 2019. Non-geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%-78.3%) and 53.3% (51.7%-54.8%) respectively (p < 0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%-51.4%) and 83.7% (82.7%-84.7%) respectively (p < 0.0001); geriatric data yielded 5YS of 29.3% (26.5%-32.1%) and 62.8% (60.8%-64.6%) respectively (p < 0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42-2.70) (p < 0.0001). CONCLUSIONS: Cancer-specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients.

Electroanalysis overview: additive manufactured biosensors using fused filament fabrication.

Additive manufacturing (3D-printing), in particular fused filament fabrication, presents a potential paradigm shift in the way electrochemical based biosensing platforms are produced, giving rise to a new generation of personalized and on-demand biosensors. The use of additive manufactured biosensors is unparalleled giving rise to unique customization, facile miniaturization, ease of use, economical but yet, still providing sensitive and selective approaches towards the target analyte. In this mini review, we focus on the use of fused filament fabrication additive manufacturing technology alongside different biosensing approaches that exclusively use antibodies, enzymes and associated biosensing materials (mediators) providing an up-to-date overview with future considerations to expand the additive manufacturing biosensors field.