Did you mean: biospecimens
-
PloS One 2024Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that causes significant late morbidity and mortality following allogeneic hematopoietic cell...
Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that causes significant late morbidity and mortality following allogeneic hematopoietic cell transplantation. The "Close Assessment and Testing for Chronic GVHD (CATCH)" study is a multi-center Chronic GVHD Consortium prospective, longitudinal cohort study designed to enroll patients before hematopoietic cell transplantation and follow them closely to capture the development of chronic GVHD and to identify clinical and biologic biomarkers of chronic GVHD onset. Data are collected pre-transplant and every two months through one-year post-transplant with chart review thereafter. Evaluations include clinician assessment of chronic GVHD and its manifestations, patient-reported outcomes, multiple biospecimens (blood, saliva, tears, buccal mucosa and fecal samples, biopsies of skin and mouth), laboratory testing, and medical record abstraction. This report describes the rationale, design, and methods of the CATCH study, and invites collaboration with other investigators to leverage this resource. trial registration: This study is registered at www.clinicaltrials.gov as NCT04188912.
Topics: Graft vs Host Disease; Humans; Hematopoietic Stem Cell Transplantation; Chronic Disease; Prospective Studies; Longitudinal Studies; Adult; Male; Female; Transplantation, Homologous; Biomarkers; Middle Aged
PubMed: 38753616
DOI: 10.1371/journal.pone.0298026 -
BMJ Open May 2024Prenatal and postnatal exposure to environmental tobacco smoke (ETS) has been linked with early childhood caries (ECC), but the specific molecular mechanisms and...
INTRODUCTION
Prenatal and postnatal exposure to environmental tobacco smoke (ETS) has been linked with early childhood caries (ECC), but the specific molecular mechanisms and pathways remain largely unknown. The Caries Risk from exposure to Environmental tobacco Smoke (CARES) within the Household Air Pollution Intervention Network (HAPIN) study aims to establish the association between ETS and ECC by employing epidemiological and novel biomarker-based approaches. Here, we outline the overall design and rationale of the project.
METHODS AND ANALYSIS
We will leverage the infrastructure and data from the HAPIN trial (India) to mount the CARES study. In this ambidirectional cohort study, children (n=735, aged: 3-5 years) will undergo ECC examination by a trained dentist using standard criteria and calibrated methods. Structured questionnaires will be used to gather information on sociodemographic variables, dietary habits, oral hygiene, oral health-related quality of life and current exposure to ETS. We will collect non-invasive or minimally invasive biospecimens (i.e., saliva, buccal cells, dried blood spots and urine) from a subset of HAPIN children (n=120) to assess a battery of biomarkers indicative of exposure to ETS, early biological effect and epigenetic modifications. Both self-reported and objective measures of ETS exposure collected longitudinally during in utero and early postnatal periods will be accessed from the HAPIN database. We will apply current science data techniques to assess the association and interrelationships between ETS, ECC, and multiple biomarkers.
ETHICS AND DISSEMINATION
Information gathered in this research will be published in peer-reviewed journals and summaries will be shared with the key stakeholders as well as patients and their parents/guardians involved in this study. Sri Ramachandra Institute of Higher Education and Research Ethics Board has approved the study protocol (IEC-NI22/JUL/83/82).
TRIAL REGISTRATION NUMBER
NCT02944682.
Topics: Humans; Tobacco Smoke Pollution; Dental Caries; Child, Preschool; Female; India; Male; Cohort Studies; Biomarkers; Research Design; Pregnancy; Prenatal Exposure Delayed Effects; Environmental Exposure; Risk Factors
PubMed: 38749682
DOI: 10.1136/bmjopen-2024-083874 -
BMJ Open May 2024Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures,...
Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) - a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health.
PURPOSE
Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk of pregnancy complications that are associated with long-term cardiometabolic risk. However, the impact of perinatal EDC exposure on subsequent cardiometabolic risk post-pregnancy is less understood. The Environmental Reproductive and Glucose Outcomes (ERGO) Study was established to investigate the associations of environmental exposures during the perinatal period with post-pregnancy parental cardiometabolic health.
PARTICIPANTS
Pregnant individuals aged ≥18 years without pre-existing diabetes were recruited at <15 weeks of gestation from Boston, Massachusetts area hospitals. Participants completed ≤4 prenatal study visits (median: 12, 19, 26, 36 weeks of gestation) and 1 postpartum visit (median: 9 weeks), during which we collected biospecimens, health histories, demographic and behavioural data, and vitals and anthropometric measurements. Participants completed a postpartum fasting 2-hour 75 g oral glucose tolerance test. Clinical data were abstracted from electronic medical records. Ongoing (as of 2024) extended post-pregnancy follow-up visits occur annually following similar data collection protocols.
FINDINGS TO DATE
We enrolled 653 unique pregnancies and retained 633 through delivery. Participants had a mean age of 33 years, 10% (n=61) developed gestational diabetes and 8% (n=50) developed pre-eclampsia. Participant pregnancy and postpartum urinary phthalate metabolite concentrations and postpartum glycaemic biomarkers were quantified. To date, studies within ERGO found higher exposure to phthalates and phthalate mixtures, and separately, higher exposure to radioactive ambient particulate matter, were associated with adverse gestational glycaemic outcomes. Additionally, certain personal care products used in pregnancy, notably hair oils, were associated with higher urinary phthalate metabolite concentrations, earlier gestational age at delivery and lower birth weight.
FUTURE PLANS
Future work will leverage the longitudinal data collected on pregnancy and cardiometabolic outcomes, environmental exposures, questionnaires, banked biospecimens and paediatric data within the ERGO Study.
Topics: Humans; Female; Pregnancy; Adult; Prospective Studies; Boston; Environmental Exposure; Endocrine Disruptors; Young Adult; Glucose Tolerance Test; Blood Glucose; Postpartum Period; Maternal Exposure; Cardiometabolic Risk Factors
PubMed: 38719310
DOI: 10.1136/bmjopen-2023-079782 -
Science Advances May 2024Viscoelastic transformation of tissue drives aberrant cellular functions and is an early biomarker of disease pathogenesis. Tissues scale a range of viscoelastic moduli,...
Viscoelastic transformation of tissue drives aberrant cellular functions and is an early biomarker of disease pathogenesis. Tissues scale a range of viscoelastic moduli, from biofluids to bone. Moreover, viscoelastic behavior is governed by the frequency at which tissue is probed, yielding distinct viscous and elastic responses modulated over a wide frequency band. Existing tools do not quantify wideband viscoelastic spectra in tissues, leaving a vast knowledge gap. We present wideband laser speckle rheological microscopy (WB-SHEAR) that reveals elastic and viscous response over sub-megahertz frequencies previously not investigated in tissue. WB-SHEAR uses an optical, noncontact approach to quantify wideband viscoelastic spectra in specimens spanning a range of moduli from low-viscosity fibrin to highly elastic bone. Via laser scanning, micromechanical imaging is enabled to access wideband viscoelastic spectra in heterogeneous tumor specimens with high spatial resolution (25 micrometers). The ability to interrogate the viscoelastic landscape of diverse biospecimens could transform our understanding of mechanobiological processes in various diseases.
Topics: Viscosity; Rheology; Humans; Elasticity; Animals; Lasers; Microscopy
PubMed: 38718128
DOI: 10.1126/sciadv.adl1586 -
Blockchain in Healthcare Today 2024Scientists use donated biospecimens to create organoids, which are miniature copies of patient tumors that are revolutionizing precision medicine and drug discovery....
INTRODUCTION
Scientists use donated biospecimens to create organoids, which are miniature copies of patient tumors that are revolutionizing precision medicine and drug discovery. However, biobanking platforms remove donor identifiers to protect privacy, precluding patients from benefiting from their contributions or sharing information that may be relevant to research outcomes. Decentralized biobanking (de-bi) leverages blockchain technology to empower patient engagement in biospecimen research. We describe the creation of the first de-bi prototype for an organoid biobanking use case.
METHODS
We designed and developed a proof-of-concept non-fungible tokens (NFTs) framework for an organoid research network of patients, physicians, and scientists within a synthetic dataset modeled on a real-world breast cancer organoid ecosystem. Our implementation deployed multiple smart contracts on Ethereum test networks, minting NFTs representing each stakeholder, biospecimen, and organoid. The system architecture was designed to be composable with established biobanking programs.
RESULTS
Our de-bi prototype demonstrated how NFTs representing patients, physicians, scientists, and organoids may be united in a privacy-preserving platform that builds upon relationships and transactions of existing biobank research networks. The mobile application simulated key features, enabling patients to track their biospecimens, view organoid images and research updates from scientists, and allow physicians to participate in peer-to-peer communications with basic scientists and patients alike, all while ensuring compliance with de-identification requirements.
DISCUSSION
We demonstrate proof-of-concept for a web3 platform engaging patients, physicians, and scientists in a dynamic research community, unlocking value for a model organoid ecosystem. This initial prototype is a critical first step for advancing paradigm-shifting de-bi technology that provides unprecedented transparency and suggests new standards for equity and inclusion in biobanking. Further research must address feasibility and acceptability considering the ethical, legal, economic, and technical complexities of organoid research and clinical translation.
PubMed: 38715762
DOI: 10.30953/bhty.v7.303 -
Frontiers in Reproductive Health 2024The Maternal and Infant Environmental Health Riskscape (MIEHR) Center was established to address the interplay among chemical and non-chemical stressors in the...
INTRODUCTION
The Maternal and Infant Environmental Health Riskscape (MIEHR) Center was established to address the interplay among chemical and non-chemical stressors in the biological, physical, social, and built environments that disproportionately impact perinatal health among Black pregnant people in a large and diverse urban area with documented disparities in the U.S.
METHODS
The MIEHR cohort is recruiting non-Hispanic Black and non-Hispanic white pregnant people who deliver their infants at major obstetric hospitals in Houston, Texas. At enrollment, all participants are asked to provide urine samples for chemical [metals, cotinine, and polycyclic aromatic hydrocarbons (PAHs)] analyses and blood samples. A subset of the cohort is asked to provide oral and vaginal swabs, and fecal samples. Questionnaire and electronic health record data gather information about residential address history during pregnancy, pregnancy history and prenatal care, sociodemographic and lifestyle factors, experiences of discrimination and stress, and sources of social support. Using information on where a participant lived during their pregnancy, features of their neighborhood environment are characterized. We provide summaries of key individual- and neighborhood-level features of the entire cohort, as well as for Black and white participants separately.
RESULTS
Between April 2021 and February 2023, 1,244 pregnant people were recruited. Nearly all participants provided urine samples and slightly less than half provided blood samples. PAH exposure patterns as assessed on 47% of participants thus far showed varying levels depending on metabolite as compared to previous studies. Additionally, analyses suggest differences between Black and white pregnant people in experiences of discrimination, stress, and levels of social support, as well as in neighborhood characteristics.
DISCUSSION
Our findings to date highlight racial differences in experiences of discrimination, stress, and levels of support, as well as neighborhood characteristics. Recruitment of the cohort is ongoing and additional neighborhood metrics are being constructed. Biospecimens will be analyzed for metals and PAH metabolites (urine samples), miRNAs (plasma samples) and the microbiome (oral swabs). Once enrollment ends, formal assessments are planned to elucidate individual- and neighborhood-level features in the environmental riskscape that contribute to Black-White disparities in perinatal health.
PubMed: 38712340
DOI: 10.3389/frph.2024.1304717 -
MedRxiv : the Preprint Server For... Apr 2024Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and...
ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.
BACKGROUND
Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes.
METHODS
In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (+/- 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 296 evaluable patients (148 per arm) will provide statistical power of 90.5% to detect an 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse effects. Biospecimens including archival tumor tissue, plasma and buffy coat in EDTA tubes, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and has a current accrual of 312. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org .
DISCUSSION
Building off of data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed the current trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer.
TRIAL REGISTRATION
Clinicaltrials.gov ID: NCT05610163 ; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).
PubMed: 38712176
DOI: 10.1101/2024.04.25.24306396 -
Frontiers in Microbiology 2024Emerging evidence demonstrates that the gastrointestinal microbiome has the potential to be a biomarker in neoadjuvant chemoradiotherapy for colorectal cancer (CRC). Yet...
BACKGROUND
Emerging evidence demonstrates that the gastrointestinal microbiome has the potential to be a biomarker in neoadjuvant chemoradiotherapy for colorectal cancer (CRC). Yet studies on the impact of the gastric microbiome (GM) on the response to neoadjuvant chemotherapy (NACT) are still scarce.
METHODS
Forty-eight patients with gastric cancer participated in this retrospective study, and 16S rRNA sequencing was performed to evaluate formalin-fixed and paraffin-embedded (FFPE) tissue biospecimens and fresh-frozen tissues.
RESULTS
In this study, 16 bacterial taxa at different levels, including , , and , were identified to be enriched before NACT in response (R) patients in group FFPE. In contrast, 6 bacterial taxa, such as , (), etc. were enriched after NACT, in which we reported for the first time that the phylum was enriched before NACT in R patients. Thirty-one bacterial taxa of , , , and were identified in group mucosa as being enriched in R patients. In comparison, 4 bacterial taxa dominated by the phylum were enriched in NR patients. Notably, the family was found in both tissue samples, and the metabolic pathways, including the citrate cycle (TCA cycle) and various amino acids, including alanine, were found to be potentially predictive in both sample species.
CONCLUSION
There are differences in the features of the GM for different NACT response results. The causal relationship deserves to be confirmed by further investigations.
PubMed: 38694796
DOI: 10.3389/fmicb.2024.1357261 -
JAMA Network Open May 2024Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about... (Observational Study)
Observational Study
IMPORTANCE
Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer.
OBJECTIVE
To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer-specific mortality.
DESIGN, SETTING, AND PARTICIPANTS
This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023.
EXPOSURES
Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ.
MAIN OUTCOMES AND MEASURES
The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer-specific mortality). The secondary outcome was prostate cancer-specific mortality.
RESULTS
Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer-specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7.
CONCLUSIONS AND RELEVANCE
In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.
Topics: Humans; Male; Prostatic Neoplasms; Disease Progression; Aged; Middle Aged; Longitudinal Studies; Diet, Vegetarian; United States; Cohort Studies; Diet, Plant-Based
PubMed: 38691361
DOI: 10.1001/jamanetworkopen.2024.9053 -
Genes Apr 2024Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.
METHODS
Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.
RESULTS
Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.
DISCUSSION
Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.
Topics: Amyotrophic Lateral Sclerosis; Humans; Neurofilament Proteins; Biomarkers; Intermediate Filaments; Prognosis
PubMed: 38674431
DOI: 10.3390/genes15040496