Molecular mechanism of distinct chemokine engagement and functional divergence of the human Duffy antigen receptor.

The Duffy antigen receptor is a seven-transmembrane (7TM) protein expressed primarily at the surface of red blood cells and displays strikingly promiscuous binding to multiple inflammatory and homeostatic chemokines. It serves as the basis of the Duffy blood group system in humans and also acts as the primary attachment site for malarial parasite Plasmodium vivax and pore-forming toxins secreted by Staphylococcus aureus. Here, we comprehensively profile transducer coupling of this receptor, discover potential non-canonical signaling pathways, and determine the cryoelectron microscopy (cryo-EM) structure in complex with the chemokine CCL7. The structure reveals a distinct binding mode of chemokines, as reflected by relatively superficial binding and a partially formed orthosteric binding pocket. We also observe a dramatic shortening of TM5 and 6 on the intracellular side, which precludes the formation of the docking site for canonical signal transducers, thereby providing a possible explanation for the distinct pharmacological and functional phenotype of this receptor.

Categorization learning induced changes in action representations in the macaque STS.

Neuroimaging and single cell recordings have demonstrated the presence of STS body category-selective regions (body patches) containing neurons responding to presentation of static bodies and body parts. To date, it remains unclear if these body patches and additional STS regions respond during observation of different categories of dynamic actions and to what extent categorization learning influences representations of observed actions in the STS. In the present study, we trained monkeys to discriminate videos depicting three different actions categories (grasping, touching and reaching) with a forced-choice action categorization task. Before and after categorization training, we performed fMRI recordings while monkeys passively observed the same action videos. At the behavioral level, after categorization training, monkeys generalized to untrained action exemplars, in particular for grasping actions. Before training, uni- and/or multivariate fMRI analyses suggest a broad representation of dynamic action categories in particular in posterior and middle STS. Univariate analysis further suggested action category specific training effects in middle and anterior body patches, face patch ML and posterior STS region MT and FST. Overall, our fMRI experiments suggest a widespread representation of observed dynamic bodily actions in the STS that can be modulated by visual learning, supporting its proposed role in action recognition.

Cancer survivorship challenges of rural older adults: a qualitative study.

BACKGROUND: Although research has advanced the field of oncologic geriatrics with survivors to assess their cancer-related needs and devise patient-centered interventions, most of that research has excluded rural populations. This study aimed to understand the survivorship challenges and recommendations in the perspective of rural older adults. METHODS: This was a qualitative study that explored the survivorship challenges and recommendations of rural older adults who have completed curative intent chemotherapy for a solid tumor malignancy in the 12 months prior to enrollment in the present study. RESULTS: Twenty-seven older adult survivors from rural areas completed open-ended semi-structured interviews. The mean age was 73.4 (SD = 5.0). Most participants were non-Hispanic White (96.3%), female (59.3%), married (63.0%), and had up to a high school education (51.9%). Rural older survivors reported a general lack of awareness of survivorship care plans, communication challenges with healthcare team, transportation challenges, financial toxicity, psychological challenges, and diet and physical challenges. Rural older survivors recommend the provision of nutritional advice referral to exercise programs, and social support groups and for their healthcare providers to discuss their survivorship plan with them. CONCLUSIONS: Although study participants reported similar survivorship challenges as urban older adult survivors, additional challenges reported regarding transportation and consideration of farm animals have not been previously reported. Heightened awareness of the survivorship needs of rural older adults may result in better survivorship care for this population.

Effect of dietary anthocyanins on biomarkers of type 2 diabetes and related obesity: A systematic review and meta-analysis.

Anthocyanins have been reported for the protective effects against type 2 diabetes and related obesity. This meta-analysis examined the benefits of anthocyanins on type 2 diabetes and obesity biomarkers in animals and humans. The study included 21 clinical trials and 27 pre-clinical studies. A systematic search was conducted using the following inclusion criteria: in vivo rodent studies; human randomized clinical trials, both aimed at assessing the fasting blood glucose (FBG), HbA1c, total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein; and study duration of at least two weeks. Out of the 201 examined publications, 48 were shortlisted after implementation of the selection criteria. Results of clinical trials demonstrated that consumption of anthocyanin-rich food significantly reduced the FBG (p < 0.0001), HbA1c (p = 0.02), TC (p = 0.010), TG (p = 0.003), LDL (p = 0.05) and increases the HDL (p = 0.03) levels. Similarly, pre-clinical studies demonstrated the amelioration of the HbA1c (p = 0.02), FBG, TC, TG, and LDL (p < 0.00001), with non-significant changes in the HDL (p = 0.11). Sub-group analysis indicated dose-dependent effect. This compilation confirms that consuming anthocyanin-rich foods positively correlates with the reduction in the blood glucose and lipid levels in diabetic and obese subjects.

A multifunctional recyclable adsorbent based on engineered MIL-125 (Ti) magnetic mesoporous composite for the effective removal of pathogens.

The elimination of pathogenic bacteria from water sources is currently crucial for obtaining drinkable water. Therefore, the development of platforms with the ability to interact with pathogens and remove them is a potential future tool for medicine, food and water safety. In this work, we have grafted a layer of NH2-MIL-125 (Ti) on Fe3O4@SiO2 magnetic nanospheres for the removal of multiple pathogenic bacteria from water. The synthesized Fe3O4@SiO2@NH2-MIL-125 (Ti) nano adsorbent was characterized by FE-SEM, HR-TEM, FT-IR, XRD, BET surface analysis, magnetization tests, respectively, which illustrated its well-defined core-shell structure and magnetic behaviour. The prepared magnetic-MOF composite sorbent was attractive towards capturing a wide range of pathogens (S. typhimurium, S. aureus, E. coli, P. aeruginosa and K. pneumoniae) under experimental conditions. Influence factors such as adsorbent dosage, bacterial concentration, pH and incubation time were optimized for enhanced bacterial capture. The application of an external magnetic field removed Fe3O4@SiO2@NH2-MIL-125 (Ti) nano adsorbent from the solution along with sweeping the attached pathogenic bacteria. The non-specific removal efficiency of S. typhimurium for magnetic MOF composite was 96.58%, while it was only 46.81% with Fe3O4@SiO2 particles. For specific removal, 97.58% of S. typhimurium could be removed selectively from a mixture with monoclonal anti- Salmonella antibody conjugated magnetic MOF at a lower concentration of 1.0 mg/mL. The developed nano adsorbent may find great potential in microbiology applications and water remediation.

Novel CIC variants identified in individuals with neurodevelopmental phenotypes.

Heterozygous pathogenic variants in CIC, which encodes a transcriptional repressor, have been identified in individuals with neurodevelopmental phenotypes. To date, 11 CIC variants have been associated with the CIC-related neurodevelopmental syndrome. Here, we describe three novel and one previously reported CIC variants in four individuals with neurodevelopmental delay. Notably, we report for the first time a de novo frameshift variant specific to the long isoform of CIC (CIC-L, NM_001304815.1:c.1100dup, p.Pro368AlafsTer16) in an individual with speech delay, intellectual disability, and autism spectrum disorder. Our investigation into the function of CIC-L reveals that partial loss of CIC-L leads to transcriptional derepression of CIC target genes. We also describe a missense variant (NM_015125.3:c.683G>A, p.Arg228Gln) in an individual with a history of speech delay and relapsed pre-B acute lymphoblastic leukemia. Functional studies of this variant suggest a partial loss of CIC transcriptional repressor activity. Our study expands the list of CIC pathogenic variants and contributes to the accumulating evidence that CIC haploinsufficiency or partial loss of function is a pathogenic mechanism causing neurodevelopmental phenotypes.

Intrinsic functional clustering of ventral premotor F5 in the macaque brain.

Neurophysiological and anatomical data suggest the existence of several functionally distinct regions in the lower arcuate sulcus and adjacent postarcuate convexity of the macaque monkey. Ventral premotor F5c lies on the postarcuate convexity and consists of a dorsal hand-related and ventral mouth-related field. The posterior bank of the lower arcuate contains two additional premotor F5 subfields at different anterior-posterior levels, F5a and F5p. Anterior to F5a, area 44 has been described as a dysgranular zone occupying the deepest part of the fundus of the inferior arcuate. Finally, area GrFO occupies the most rostral portion of the fundus and posterior bank of inferior arcuate and extends ventrally onto the frontal operculum. Recently, data-driven exploratory approaches using resting-state fMRI data have been suggested as a promising non-invasive method for examining the functional organization of the primate brain. Here, we examined to what extent partitioning schemes derived from data-driven clustering analysis of resting-state fMRI data correspond with the proposed organization of the fundus and posterior bank of the macaque arcuate sulcus, as suggested by invasive architectonical, connectional and functional investigations. Using a hierarchical clustering analysis, we could retrieve clusters corresponding to the dorsal and ventral portions of F5c on the postarcuate convexity, F5a and F5p at different antero-posterior locations on the posterior bank of the lower arcuate, area 44 in the fundus, as well as part of area GrFO in the most anterior portion of the fundus. Additionally, each of these clusters displayed distinct whole-brain functional connectivity, in line with previous anatomical tracer and seed-based functional connectivity investigations of F5/44 subdivisions. Overall, our data suggests that hierarchical clustering analysis of resting-state fMRI data can retrieve a fine-grained level of cortical organization that resembles detailed parcellation schemes derived from invasive functional and anatomical investigations.

Assessing the bioremediation potential of indigenously isolated Klebsiella sp. WAH1 for diclofenac sodium: optimization, toxicity and metabolic pathway studies.

Among the various pharmaceutical pollutants, diclofenac sodium (DFS), a widely prescribed non-steroid anti-inflammatory drug is detected in the aquatic environment at concentrations which can be harmful to living organisms. Present study illustrates the isolation and characterization of strain Klebsiella pneumoniae WAH1 from activated sludge and its ability to degrade DFS as sole source of carbon and energy. The growth and degradation capacity of K. pneumoniae WAH1 under different conditions of pH, temperature, rotation speed, and inoculum age were evaluated using optical density and liquid chromatography-mass spectroscopy (LCMS). The results show that K. pneumoniae WAH1 can grow well with DFS as its sole source of carbon and degrade 79.14% of DFS (10 mg L-1) within 72 h. Based on chemical structure of intermediates detected through LCMS, it is inferred that degradation pathway advanced by hydroxylation, decarboxylation, and dechlorination reactions. Toxicity studies revealed the non-toxic nature of the end-products of DFS degradation after 72 h. The findings suggest that K. pneumoniae WAH1 has an excellent potential for bioremediation of DFS in industrial wastewaters.

Influence of Biofortified Colored Wheats (Purple, Blue, Black) on Physicochemical, Antioxidant and Sensory Characteristics of Chapatti (Indian Flatbread).

Biofortified colored wheat (black, blue, and purple) is rich in anthocyanins and phenolic acid compounds that impart positive physiological effects in humans. A large proportion of wheat is consumed in the form of Chapatti in Asian countries. The effect of chapatti cooking on the proximate composition, bioactive compounds (anthocyanins and phenolics), and antioxidant activities of these wheat varieties were checked in this study. Apart from acceptable sensory parameters, good taste, and soft texture of chapatti, biofortified colored wheat chapatti and flour had higher dietary fibers, protein content, and lower carbohydrate content. Higher soluble and insoluble phenolic compounds, anthocyanin content, and antioxidant activity were in the order of black > blue > purple > white. Chapatti making has reduced their antioxidant activity and anthocyanin content in comparison to flour. Moreover, the reduction in antioxidant activity is less as compared to the decrease in anthocyanin content. Our results suggest that colored wheat can be a better alternative to normal wheat for preparing chapatti as it would have additional health-promoting activities.

Direct shoot organogenesis from leaf explants of Populus deltoides and changes in selected enzymatic activities.

The direct shoot organogenesis was achieved from leaf explant of two commercially important clones of Populus deltoides on MS medium enriched with 15 mg/l adenine sulphate, 5 mg/l Ascorbic acid, 250 mg/l (NH4)2SO4 (referred to as PD1 medium) supplemented with 2.5 µM each of 6-benzylaminopurine and indole-3-acetic acid. Higher shoot organogenic potential was recorded from the explants of clone 'G48' as compared to clone 'L34'. The age of leaf explant also affected the shoot organogenic potential, and maximum shoot organogenesis was recorded in case of 5th leaf from the top of microshoot. Histological studies revealed altered cell division resulting in the formation of meristematic pockets after 5 days of culture, these meristematic pockets grew into dome protuberances by 10th day. Organized shoots were visible after 15 days of culture. A clear three phases of shoot organogenesis viz induction (0-4 days), initiation and organization (4-10 days) and growth (11-16 days onwards) were observed. Marked variation in the activity of enzymes such as catalase, peroxidase, polyphenol oxidase and acid phosphatase was observed during these phases. The activity of these enzymes was found to increase in cultures grown on the medium resulting in shoot organogenesis during shoot development (after 7 days of culture).

Functional MRI Responses to Passive, Active, and Observed Touch in Somatosensory and Insular Cortices of the Macaque Monkey.

Neurophysiological data obtained in primates suggests that merely observing others' actions can modulate activity in the observer's motor cortices. In humans, it has been suggested that these multimodal vicarious responses extend well beyond the motor cortices, including somatosensory and insular brain regions, which seem to yield vicarious responses when witnessing others' actions, sensations, or emotions (Gazzola and Keysers, 2009). Despite the wealth of data with respect to shared action responses in the monkey motor system, whether the somatosensory and insular cortices also yield vicarious responses during observation of touch remains largely unknown. Using independent tactile and motor fMRI localizers, we first mapped the hand representations of two male monkeys' primary (SI) and secondary (SII) somatosensory cortices. In two subsequent visual experiments, we examined fMRI brain responses to (1) observing a conspecific's hand being touched or (2) observing a human hand grasping or mere touching an object or another human hand. Whereas functionally defined "tactile SI" and "tactile SII" showed little involvement in representing observed touch, vicarious responses for touch were found in parietal area PFG, consistent with recent observations in humans (Chan and Baker, 2015). Interestingly, a more anterior portion of SII, and posterior insular cortex, both of which responded when monkeys performed active grasping movements, also yielded visual responses during different instances of touch observation.SIGNIFICANCE STATEMENT Common coding of one's own and others' actions, sensations, and emotions seems to be widespread in the brain. Although it is currently unclear to what extent human somatosensory cortices yield vicarious responses when observing touch, even less is known about the presence of similar vicarious responses in monkey somatosensory cortex. We therefore localized monkey somatosensory hand representations using fMRI and investigated whether these regions yield vicarious responses while observing various instances of touch. Whereas "tactile SI and SII" did not elicit responses during touch observation, a more anterior portion of SII, in addition to area PFG and posterior insular cortex, all of which responded during monkeys' own grasping movements, yielded vicarious responses during observed touch.

Investigating common coding of observed and executed actions in the monkey brain using cross-modal multi-variate fMRI classification.

Mirror neurons are generally described as a neural substrate hosting shared representations of actions, by simulating or 'mirroring' the actions of others onto the observer's own motor system. Since single neuron recordings are rarely feasible in humans, it has been argued that cross-modal multi-variate pattern analysis (MVPA) of non-invasive fMRI data is a suitable technique to investigate common coding of observed and executed actions, allowing researchers to infer the presence of mirror neurons in the human brain. In an effort to close the gap between monkey electrophysiology and human fMRI data with respect to the mirror neuron system, here we tested this proposal for the first time in the monkey. Rhesus monkeys either performed reach-and-grasp or reach-and-touch motor acts with their right hand in the dark or observed videos of human actors performing similar motor acts. Unimodal decoding showed that both executed or observed motor acts could be decoded from numerous brain regions. Specific portions of rostral parietal, premotor and motor cortices, previously shown to house mirror neurons, in addition to somatosensory regions, yielded significant asymmetric action-specific cross-modal decoding. These results validate the use of cross-modal multi-variate fMRI analyses to probe the representations of own and others' actions in the primate brain and support the proposed mapping of others' actions onto the observer's own motor cortices.

Malignant melanoma in early-treated Parkinson's disease: the NET-PD trial.

BACKGROUND: The risk for malignant melanoma is higher than expected in Parkinson's disease (PD). The National Institutes of Health (NIH) Exploratory Trials in PD (NET-PD) Long-term Study 1 (LS-1) trial is a contemporary phase 3 study of subjects with early, treated PD. The objective of this work was to assess the incidence of malignant melanoma in a PD cohort. METHODS: Incident melanoma cases were identified from the adverse events log. The expected number of cases was calculated, using the expected incidence rates and the number of person-years. RESULTS: A total of 618 females and 1119 males were followed for 6452 person-years; 19 new melanoma cases were observed. The expected number was 5.29. The standardized event ratio compared to the general population was 3.6 (95% confidence interval, 2.2-5.6). CONCLUSIONS: The risk for developing melanoma was higher than expected in the NET-PD LS-1 cohort and was similar to the risk reported in earlier comparable clinical trial cohorts. Dermatologic screening may be useful in Parkinson's disease to identify melanoma at an early stage.

Feature-selective responses in macaque visual cortex follow eye movements during natural vision.

In natural vision, primates actively move their eyes several times per second via saccades. It remains unclear whether, during this active looking, visual neurons exhibit classical retinotopic properties, anticipate gaze shifts or mirror the stable quality of perception, especially in complex natural scenes. Here, we let 13 monkeys freely view thousands of natural images across 4.6 million fixations, recorded 883 h of neuronal responses in six areas spanning primary visual to anterior inferior temporal cortex and analyzed spatial, temporal and featural selectivity in these responses. Face neurons tracked their receptive field contents, indicated by category-selective responses. Self-consistency analysis showed that general feature-selective responses also followed eye movements and remained gaze-dependent over seconds of viewing the same image. Computational models of feature-selective responses located retinotopic receptive fields during free viewing. We found limited evidence for feature-selective predictive remapping and no viewing-history integration. Thus, ventral visual neurons represent the world in a predominantly eye-centered reference frame during natural vision.

Polyacrylonitrile as a versatile matrix for gold nanoparticle-based SERS substrates.

As an effective and ultrasensitive molecule detection technique, surface-enhanced Raman spectroscopy (SERS) needs efficient and highly responsive substrates to further enhance its sensitivity and utility. In this work, the preparation and characterisation of polyacrylonitrile/gold nanoparticle (PAN/AuNPs) composite porous films have been described for SERS-based detection of methylene blue (MB) dye. The PAN/AuNPs composite films were prepared with a simple dip coating technique, yielding a highly porous structure with uniformly dispersed Au nanoparticles (AuNPs). Scanning electron microscopy (SEM) revealed a linked pore network within the films. In X-ray diffraction (XRD), the characteristic crystal peak of AuNP clusters was observed, proving the presence of AuNPs in the composite. UV-vis absorption spectra also indicated the existence of the AuNPs. The methylene blue (MB) dye has been detected using PAN/AuNPs composite SERS substrates. These substrates showed excellent sensitivity by detecting 50 nM dye concentration and enhancing the Raman peak intensity at 1622 cm-1. The SERS enhancement factor (EF) for MB detection was determined to be around 106, demonstrating the remarkable sensitivity of the PAN/AuNPs composite porous films. The findings demonstrate the enormous potential of PAN/AuNPs composite porous films as reliable SERS substrates, displaying their efficacy in detecting trace levels of analytes in chemical and biological sensing applications.

Simple fluorochromic detection of chromium with ascorbic acid functionalized luminescent Bio-MOF-1.

The bioaccumulation of various heavy metals in the environment and agriculture is posing serious hazards to human health. Hexavalent chromium is one of the most encountered heavy metal pollutants. The routine monitoring of Cr(VI) via simple methods assumes great analytical significance in sectors like environmental safety, food quality, etc. This study reports a novel biocompatible and luminescent metal-organic framework (ascorbic acid functionalized Bio-MOF-1) based "Turn-on" nanoprobe for rapid and sensitive optical detection of Cr(VI). Bio-MOF-1 has been synthesized, functionalized with ascorbic acid (AA), and then comprehensively characterized for its key material properties. The presence of Cr(VI) results in the photoluminescence recovery of Bio-MOF-1/AA. Using the above approach, Cr(VI) is detected over a wide concentration range of 0.02 to 20 ng mL-1, with the limit of detection being 0.01 ng mL-1. The nanoprobe is capable of detecting Cr(VI) in real water as well as in some spiked food samples. Hence, the ascorbic acid functionalized Bio-MOF-1 nanoprobe is established as a potential on-field detection tool for Cr(VI).

Impact of in-hospital statin use on mortality in COVID-19 patients from a majority African American population.

BACKGROUND: The COVID-19 pandemic has claimed over 6.4 million lives globally. Finding effective medications to reduce mortality in hospitalized COVID-19 patients remains critical. No previous study has been published on the effects of statin use in a majority African American COVID-19 patient population. OBJECTIVE: This study aims to assess the relationship between in-hospital statin use and mortality in this population. METHODS: A retrospective chart review of patients diagnosed with COVID-19 from March 2020 to June 2020 admitted to the Phoebe Putney Health System in Albany, Georgia, an early epicenter of the COVID-19 pandemic, was conducted. The outcomes of 735 hospitalized COVID-19 positive patients from over 40 counties in Georgia were analyzed. The primary outcome of interest was all-cause mortality, with secondary outcomes of interest of ICU care, length of ICU stay, need for mechanical ventilator, duration of intubation, and need for dialysis. Multivariate logistic regression and Cox proportional hazards analysis were conducted to examine the effect of in-hospital statin use and mortality. RESULTS: 186 of 735 total patients were prescribed statins in-hospital. 83.8% were African American. Multivariate logistic regression found in-hospital statin use was not significantly associated with the primary outcome - all-cause mortality (p=0.23). Similar findings were seen in need for ICU care, length of ICU stay, need for mechanical ventilator, duration of intubation, and need for dialysis (p>0.05). Additionally, results from a Cox proportional hazards model found in-hospital statin use was not associated with survival time. Sensitivity analysis conducted on only African American patients validated that in-hospital statin use was not associated with all-cause mortality in these patients. Of note, immunosuppression and severe disease presentation were associated with a six-fold increase in risk of mortality and the largest decreases in survival time. CONCLUSION: It is possible statins have no mortality benefit for this patient population, but further research beyond this association study would need to be conducted to determine this conclusively. From this study, the best clinical recommendation would be to continue statins for COVID-19 patients with pre-hospital statin use and to launch a randomized clinical trial to definitively determine the efficacy of statins in the treatment of hospitalized COVID-19 patients.

Observational evidence of changing cloud macro-physical properties under warming climate over the Indian summer monsoon region.

The cloud responses to global warming are captured in various global climate models with distinct inferences on changes in cloud vertical structure as function of surface warming. However, long term observational evidences are scarce to validate the model outputs. Here, we have studied the changes in radiosonde derived cloud macro-physical properties and their association with other atmospheric variables during the period 2000-2019 in response to warming climate over the Indian summer monsoon region. We have observed a statistically significant increase in the frequency of cloudy days (∼13 % decade-1), high-level clouds (HLCs ∼11 % decade-1) and simultaneous decrease in low-level clouds (LLCs ∼8 % decade-1) over the Indian region during the monsoon season. The multiple linear regression, principle component analyses and further correlation analyses suggest significant associations between cloud vertical structure variations and large-scale climate indicators, such as global warming and El Niño-Southern Oscillation. The vertical extension of the tropospheric column and the upward shift of clouds, attributed to global warming, explain the changes observed in both HLCs and LLCs. These results contribute to a deeper understanding of the dynamic interplay between global climate change and regional cloud dynamics, with implications for weather and climate modeling.

Barriers to participation in clinical trials of rural older adult cancer survivors: A qualitative study.

BACKGROUND: Currently, 64% of cancer survivors are aged 65+. Older cancer survivors have unique complications after chemotherapy and are often excluded from cancer clinical trials. Although there is research on barriers to clinical trial participation of older adult cancer survivors, to date no research has explored barriers to clinical trial participation unique to rural older adult cancer survivors. METHODS: This study is a secondary qualitative analysis from a study exploring survivorship challenges of rural older adults. Eligible participants were rural residents over age 65 who have completed curative-intent chemotherapy in the past 12 months. Participants (n = 27) completed open-ended semi-structured interviews that included questions on barriers to clinical trial participation. Transcripts were coded independently by two coders using thematic analysis. We have adhered to the standards for reporting qualitative research. FINDINGS: Participants reported a variety of barriers that included limited knowledge and fear about clinical trials, transportation challenges, their physicians not informing them of clinical trials, and thinking they are too old to participate in clinical trials. However, participants also reported facilitators to participating in clinical trials, including acknowledging benefits to their own health and society, and understanding the importance of clinical trials. CONCLUSION: Rural older cancer survivors face numerous interpersonal, intrapersonal, and organizational barriers to clinical trial participation. Aging- and location-sensitive interventions that focus on patients, their caregivers, and health care providers may lead to improved participation of rural older adult survivors into clinical trials.

Development and Evaluation of a Multisource Approach to Extend Mortality Follow-Up for Older Adults With Advanced Cancer Enrolled in Randomized Trials.

PURPOSE: Mortality data can complement primary end points from cancer clinical trials. Yet, identifying deaths after trial completion is challenging, as timely and comprehensive vital status data are unavailable in the United States. We developed and evaluated a multisource approach to capture death data after clinical trial completion. METHODS: Individuals age 70 years and older with incurable solid tumors or lymphoma and ≥1 aging-related condition were enrolled from October 2014 to March 2019 (ClinicalTrials.gov identifier: NCT02107443 and NCT02054741). Participants provided consent to link trial information to external sources. We developed a stepped approach for extended death capture using (1) active trial follow-up up to 1 year, (2) linkage to the National Death Index (NDI), and (3) obituary searches, thus generating a 5-year survival curve. In a random sample of 50 participants who died during trial follow-up, we estimated sensitivity of death data using NDI and obituary sources and computed survival times by data source. RESULTS: The two trials enrolled 1,169 participants; mean age was 76 years; 46% were female; and gastrointestinal cancer (30%) and lung cancer (26%) were the most common cancer types. Across data sources, maximum follow-up was >7 years; 5-year survival was 18%. In total, there were 841 deaths: 603 identified during trial follow-up; 199 from the NDI; and 39 from obituary searches. The sensitivity for death capture was 92% for the NDI and 94% for the obituary searches compared with the trial data, and computed survival times were similar across data sources. CONCLUSION: Extending clinical trial mortality follow-up through linkage with external data sources was feasible and accurate. Future cancer clinical trials should collect necessary consent and patient identifiers for vital status linkages that can enhance understanding of longer-term outcomes.