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Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.
PMC10240679
Declarations
PMC10240679
Ethics approval consent to participate
The ethical review board of Fayoum University Hospital approved the study design before the start of the study (M 546). The methods were done according to the relevant guidelines and regulations. Written informed consent was obtained from all patients.
PMC10240679
Consent for publication
Written informed consent was obtained from all patients.
PMC10240679
Competing interests
The authors declare no competing interests.
PMC10240679
References
PMC10240679
Subject terms
IgAN, proteinuria
IGA NEPHROPATHY
We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional, open-label, single-arm, non-randomized study that enrolled 32 patients with IgAN at high risk of progression (BUDIGAN study, ISRCTN47722295, date of reg...
PMC10656480
Introduction
IgAN, primary glomerular disease
PATHOGENESIS, IMMUNOGLOBULIN A NEPHROPATHY
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease worldwideThe efficacy of immunosuppression in the management of IgAN remains highly controversialThe gut-kidney axis hypothesis has been supported by several studies over the past decades to underlie the pathogenesis of IgANAccordingly, w...
PMC10656480
Material and methods
PMC10656480
Study design and population
IgAN, proteinuria, primary IgAN
The BUDIGAN study (ISRCTN47722295, date of registration 14/02/2020) is a prospective, interventional, open-label, non-randomized study that enrolled 32 patients with IgAN, at high risk of progression. The study design is in line with our previous reportThe inclusion criteria were: age ≥ 18 years, patients with a histol...
PMC10656480
Treatment
proteinuria
All patients had received a stable dose of an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy for a period of at least 3 months prior to budesonide initiation. The dose of ACEI/ARB was titrated to a maximum tolerated dose in order to achieve a target blood pressure (BP) of 12...
PMC10656480
Study follow-up and data collection
The study follow-up period was 36 months. At baseline the following data were collected: age, gender, mean arterial pressure, renal function assessed by serum creatinine and eGFR (estimated glomerular filtration rate calculated by the 2009 CKD-EPI equation
PMC10656480
Study outcomes
proteinuria
ADVERSE EVENTS
The efficacy study outcomes were the effects of Budenofalk on proteinuria and eGFR at 12, 24 and 36 months. The safety outcomes were treatment emergent adverse events.
PMC10656480
Statistical analysis
±
Continuous variables were expressed as either mean (± standard deviation or 95% confidence interval) or median (interquartile range, IQR: 25th–75th percentiles) and categorical variables as percentages. Differences between groups were assessed in case of continuous variables by Student Statistical analyses were perform...
PMC10656480
Results
PMC10656480
Adverse events
gastro-intestinal bleeding, osteonecrosis
OSTEONECROSIS, ADVERSE EVENT, DIABETES MELLITUS, BLOOD, ARTERIAL HYPERTENSION
Overall, the 24-month treatment with budesonide was well tolerated (Table Adverse events.In addition, there were no patients with new-onset diabetes mellitus, gastro-intestinal bleeding, osteonecrosis or worsening of preexisting arterial hypertension. The blood glucose levels and mean arterial pressures remained stable...
PMC10656480
Author contributions
Concept/design: all authors. Data analysis/interpretation: B.O., G.I. Statistics: B.O. Data collection: all authors. Drafting article: B.O, G.I. Critical revision of article: all authors. Approval of article: G.I.
PMC10656480
Data availability
All data generated or analyzed during this study are included in this published article.
PMC10656480
Competing interests
The authors declare no competing interests.
PMC10656480
References
PMC10656480
Background
cancer
CANCER, SECONDARY
There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if inst...
PMC10108500
Methods
Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, a...
PMC10108500
Results
Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a prev...
PMC10108500
Conclusions
Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes.
PMC10108500
Trial registration
clinicaltrials.gov, NCT04614662. Registered 04/11/2020,
PMC10108500
Supplementary Information
The online version contains supplementary material available at 10.1186/s12885-023-10835-0.
PMC10108500
Keywords
PMC10108500
Background
cancer [, toxicities, cancer-
Supportive care for pediatric oncology patients focuses on preventing and managing cancer- and treatment-related toxicities. Early assessment and intervention for these toxicities are important as they are associated with morbidity, reduced quality of life, increased healthcare utilization and treatment-related mortali...
PMC10108500
Methods
The study was approved by the Research Ethics Board of The Hospital for Sick Children (SickKids), the Western Institutional Review Board and the Institutional Review Boards of each participating institution. For patient participation in the trial, informed written consent was obtained from participants and from the par...
PMC10108500
Development of symptom management care pathway templates
cancer
CANCER, PEDIATRIC CANCER
This study was focused on the management of the 15 symptoms captured by the Symptom Screening in Pediatrics Tool (SSPedi). SSPedi is a reliable, valid and responsive self-report symptom assessment tool for English, French and Spanish-speaking children and adolescents 8–18 years of age receiving cancer treatments [The a...
PMC10108500
Institutional adaptation of symptom management care pathway templates
Fig.  Phases Required to Adapt the 14 Care Pathway Templates at Each of the 10 Institutions For each statement, the institutional adaptation team made the decision to adopt, adapt or reject the statement regardless of whether the source CPG recommendation was strong or conditional. For statements stemming from condit...
PMC10108500
Survey of institutional characteristics
The creation, distribution and results of the baseline survey have previously been described [In addition to these characteristics, we administered the Consolidated Framework for Implementation Research (CFIR) to help understand factors associated with care pathway adaptation decisions [
PMC10108500
Statistics
SECONDARY
The primary aim was descriptive. The secondary aim evaluated the adaptation decision made for each of the statements on the symptom management care pathway templates and did not include new statements added by the institution. This outcome was dichotomized as reject vs. did not reject for each statement. The institutio...
PMC10108500
Results
nausea, anger, vomiting, pain, mucositis
MUCOSITIS
Table  Characteristics of Institutions (N = 10)Abbreviation: IQR - interquartile rangeFigure Table  Distribution of Statements and Adaptation Choices across 10 Institutions (N = 1350 Statements*)* Denominator for adaptation choice was the number of statements on the template care pathways (N = 1350); new statements add...
PMC10108500
Discussion
PEDIATRIC CANCER
We created 14 pediatric cancer symptom management care pathway templates based on CPGs and developed a process to adapt them at 10 institutions. We found that most care pathway statements were adopted or adapted, with 6.4% of statements being rejected. Most commonly, the reason for statement rejection was not agreeing ...
PMC10108500
Conclusions
In conclusion, acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process for 14 care pathways was accomplished in a relatively short timeframe, with a median time to accomplish the initial care pathway adaptation decision-making phase over 4.2 weeks per instit...
PMC10108500
Acknowledgements
We would like to thank the following co-leaders of the institutional adaptation teams for their work in adapting the care pathways: Nkechi Mba MD, Alexis Lemke RN, Claudette Vicks RN, Cherie Hadley RN, Andrew Cluster MD, Marissa Henning PharmD, Allison Bechtel MD, Dee Ann Omatsu NP and Nelda Itzep MD. We would also lik...
PMC10108500
Author contributions
LLD, MR
EV, FS, AK, LY, CA, CB, VA, RN, KK, DF, EO, SB, WK, MR, LLD, LS participated in all phases of the Institutional Adaptation of Symptom Management Care Pathway Templates. EV, LK, MB, AG, GT, LLD and LS were involved in material design and procedures. LS drafted the manuscript, all authors reviewed, revised and approved t...
PMC10108500
Funding
ONCOLOGY
LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. The study was supported by operating grants from the Canadian Institutes of Health Research (PJT 169165) and the National Institutes of Health (1R01CA251112).
PMC10108500
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10108500
Declarations
PMC10108500
Ethics approval and consent to participate
The study was approved by the Research Ethics Board of The Hospital for Sick Children (SickKids), the Western Institutional Review Board and the Institutional Review Boards of each participating institution. All research was performed in accordance with the Declaration of Helsinki. Agreement to be an institutional adap...
PMC10108500
Consent for publication
Not applicable.
PMC10108500
Competing interest
The authors declare that they have no competing interests.
PMC10108500
Abbreviations
Clinical practice guidelineSupportive care Prioritization, Assessment and Recommendations for KidsSymptom Screening in Pediatrics ToolConsolidated Framework for Implementation ResearchInterquartile range
PMC10108500
References
PMC10108500
Abstract
ADHESION
Editor: Linda WangAssociate Editor: Karin Hermana NepplenbroekConflicts of InterestThe authors declare no competing interests.Periodontal regeneration faces multiple challenges, the most important being cellular insufficiency. In an attempt to improve defect cellularity, we aimed to demonstrate enhancing cellular attra...
PMC10786453
Methodology
periodontitis, PD
PERIODONTITIS, SECONDARY, PLAQUE
Forty-five intrabony defects were selected from patients with stage III or IV - grade A or B periodontitis and divided randomly into three equal groups of 15 each: group1 (G1): received minimally invasive surgical technique (MIST) alone, group2 (G2): received MIST and placebo hydrogel injection, and group3 (G3): were ...
PMC10786453
Results
PD
Significant improvements in DBF, CAL, and PD were observed in the three studied groups 6 months following therapy compared to baseline (p<0.05). A significant improvement in DBF was reported in G3 compared to G1 and 2 (p=0.005). Additionally, a significantly higher CAL gain was reported in G3 compared to that of G1 (p...
PMC10786453
Conclusion
RGD peptide carried on a hydrogel delivery agent and contained with a minimally invasive flap could be a reliable option in improving the outcomes of periodontal therapy.
PMC10786453
Introduction
ADHESION, RECRUITMENT
Periodontal regeneration is a complex process that involves coordinated activities and interactions of many cell types, extracellular matrix, cytokines, and specific growth factors to restore tissue integrity. The most important challenge facing periodontal regeneration is cellular insufficiency.Apoptosis is initiated ...
PMC10786453
Methodology
PMC10786453
Population
MAY
This randomized double-blinded controlled clinical trial included 45 patients, each contributing with one periodontal intrabony defect. Patients were selected from the Medicine, Oral Diagnosis, & Periodontology Department of the Faculty of Dentistry, Minia University outpatient clinic from May 2020 to December 2021. Th...
PMC10786453
Inclusion and exclusion criteria
PERIODONTITIS
Patients were included based on the following criteria: 1- Medically free, from both sexes, and in the age range of 20-55 years old. 2- Stage III or IV, grade A or B periodontitis.
PMC10786453
Randomization, allocation, and blinding
Participants were randomly assigned using a computerized random number generator (Available from: www.random.org) into three parallel groups, with 15 participants each. Group 1: intrabony defect sites underwent MIST alone. Group 2: underwent MIST and placebo hydrogel injections. Group 3: underwent MIST and RGD hydrogel...
PMC10786453
Consort diagram for the study
PMC10786453
Sample size calculation
Power analysis was designed to have appropriate power to apply a statistical test of the null hypothesis, which implied that no difference would be found in bone healing between different groups. By adopting an alpha level of (0.05) a beta of (0.2), i.e., power=80% and an effect size (f) of (0.479), calculated based on...
PMC10786453
Interventions
PMC10786453
Hydrogel preparation
A total of 50 mg of Carbopol® 940 (Lubrizol Corporation, US) was impregnated in 10 ml water, remaining under a magnetic stirrer until completely dissolved. pH and viscosity were adjusted with triethanolamine (TEA) until the required viscosity was approximately reached (40,000–60,000 mPa-s).
PMC10786453
Preparation of 2.5 mM RGD
A total of 10 mg of RGD
PMC10786453
Pre-surgical preparation
bleeding
BLEEDING, PLAQUE
Supra and subgingival instrumentation were performed using a universal curette and ultrasonic instrument (woodpecker U600, KMC). Pre-surgical preparation was performed following the EFP S3 guidelines.20 Step 1: full mouth supragingival scaling in one visit together with patient education and oral hygiene instructions. ...
PMC10786453
Outcome measures
SECONDARY
Clinical and radiographic parameters were obtained four weeks after (S2) Phase 1 therapy was completed (baseline) and six months after surgery. The primary outcome was the evaluation of clinical attachment level (CAL), defect base fill (DBF), crestal bone level (CBL), and defect width (DW). The secondary outcomes were ...
PMC10786453
(A) MIST for 2-wall intrabony defect incision; (B) RGD loaded hydrogel application; (C) baseline radiographic measures of CEJ-BD= 9.10 mm; (D) radiographic width of bone defect= 2.3 mm; (E) radiographic measures of CEJ-BC= 4.44 mm; (F) defect angle= 39.44°
PD
Probing Depth (PD): measurements were recorded by UNCBiochemical evaluation: Gingival Crevicular Fluid (GCF) samples were collected by paper point size 30 (META BIOMED
PMC10786453
Surgical intervention
Selected sites were anesthetized using articaine HCl 4% with adrenaline (1:100,000) (Artinibsa, inibsaSpain, wedjat pharma). A minimally invasive surgical flap was performed as described by Cortellini and Tonetti
PMC10786453
Data analysis
Numerical data were presented as mean and standard deviation values. They were tested for normality using Shapiro-Wilk’s test. PI and GI were non-parametric and were analyzed using Kruskal-Wallis test. Radiographic changes in bone defect (CEJ-BD, crestal bone level, and defect width) were statistically analyzed by pair...
PMC10786453
Results
PMC10786453
Study population
In this double-blinded randomized clinical trial, 45 patients were enrolled and divided into three groups, all patients bone loss/ age were calculated to be ≤ 1. Group 1, MIST alone, was performed for 15 sites (8 males and 7 females with a mean age of 34.80±7.07); Group 2, MIST + placebo hydrogel applied in 15 sites (5...
PMC10786453
Demographic characteristics
PMC10786453
Radiographic outcomes (primary outcomes)
Significant differences between baseline and 6-month measurements of DBF were observed in all groups (
PMC10786453
Radiographic measures after 6 months follow up. (A) defect bone fill after 6 months= 4.69 mm; (B) defect width= 1.69 mm; (C) crestal bone formation= 2.31 mm; (D) angle measure= 29.14°
PMC10786453
Plaque index and gingival index
After six months, no significant differences were reported for GI and PI scores. The PI mean was reported to be (0.4±0.7) in Group 1 and (0.4±0.52 and 0.4±0.52) in Groups 2 and 3, respectively. There was no statistically significant difference between baseline and 6-month follow-up between the three groups (p > 0.05) a...
PMC10786453
Mean PI and GI data at baseline and 6 month evaluation periods
PMC10786453
Clinical attachment Level and pocket depth outcomes
Clinical attachment level and pocket depth showed a significant reduction from baseline to 6-month measurements in the three studied groups (p value= 0.000*). In G1 mean CAL reduced from 8.9±0.99 to 4.3±0.95, group 2 from 8.8±1.48 to 4.1±0.74 and in G3 from 9.5±1.08 to 3.5±0.53. A statistically significant higher reduc...
PMC10786453
Changes in clinical and radiographic parameters over time and comparisons between groups
PMC10786453
Biochemical outcomes of BMP-2 release profile
Gingival crevicular fluid BMP-2 levels showed a significant increase in its level throughout the selected evaluation periods in all groups. In G1, there was an increase from a mean of 223.85±7.27 on day 1, to 307.64±16.98 on day 7 and 333.15±31.62 on day 14, reaching the optimum level on day 21 with a mean level of 358...
PMC10786453
Changes in BMP-2 - intragroup comparisons and comparisons between groups over time
PMC10786453
Discussion
necrosis
BLOOD CLOT, ADHESION, COLLAPSE, NECROSIS, CREST
The main three elements required for optimal regeneration are defect stability, space maintenance, and enhanced cellular and mediators’ availability. The present study suggested a combination of MIST—supposed to provide reliable defect stability, space maintenance, and growth factors containment—with RGD adhesion prote...
PMC10786453
Conclusion
ADHESION
Within the limitations of this study, which, to the best of our knowledge, is the first study that evaluated the clinical and biochemical significance of RGD hydrogel in periodontal regeneration, we can conclude that the use of RGD peptide-loaded hydrogel could be an effective treatment option that improved periodontal...
PMC10786453
Acknowledgment
Thanks to Prof. Dr. Usama Farghaly, professor of Pharmaceutics, Faculty of Pharmacy, Minia University, for his cooperation, time, and patience throughout this work.Data availability statementAll data generated and analyzed during this study are included in this published article.
PMC10786453
References
PMC10786453
Subject terms
tumor, tumors, RAS-mutant unresectable, CRC
METASTATIC COLORECTAL CANCER, SECONDARY, TUMORS, TUMOR
Although patients with microsatellite instable metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single-arm, phase 1b/2 MEDITREME trial evaluated the safety and efficacy of durv...
PMC10427431
Main
CRC
METASTATIC COLORECTAL CANCER, METASTASES, INFILTRATES
Treatment of metastatic colorectal cancer (CRC) relies mainly on chemotherapy, generally for palliative purposes when metastases cannot be removed. Median overall survival (OS) of CRC has been rising with improvements in chemotherapeutic and targeted therapiesMany studies have underlined that the immune system recogniz...
PMC10427431
Results
PMC10427431
Patient characteristics
unresectable metastatic RAS-mutated CRC
Overall, 57 patients with unresectable metastatic RAS-mutated CRC were included from eight French hospitals between 30 August 2017 and 20 December 2019 (Extended Data Fig.
PMC10427431
Feasibility and safety
ADVERSE EVENT
Adverse events (AEs) occurred in 56 (98%) patients (Extended Data Table
PMC10427431
Efficacy analyses
tumors
SECONDARY, TUMORS
Among the 57 patients, MSS status was known for 51 patients; three had MSI status; and 48 had MSS status. Only the 48 patients with MSS tumors were included in the eligible population for efficacy analyses, per protocol. Median follow-up was 36 months (2.5–33.9). The primary objective of phase 2 was met, with 3-month P...
PMC10427431
Exploratory analysis of genomic correlates
NRAS
APC
Somatic panel to confirm NRAS, KRAS and BRAF mutation and MSI status was performed for all patients. Exome sequencing was performed in 37 patients. The most frequent mutations were APC, KRAS and TP53 (Fig.
PMC10427431
Exploratory analysis of transcriptome correlates
RNA sequencing (RNA-seq) analysis was performed for 36 patients. The relationships between median PFS and expression of individual protein-coding genes were tested using differential gene analysis. Using ssGSEA, EMT signature, IL6/JAK/STAT3 signature and CAF signature showed a borderline relationship with shorter PFS, ...
PMC10427431
Exploratory analysis of immunological correlates
CPS
PD-L1 CPS expression was not related to outcome (Extended Data Fig.
PMC10427431
Analysis of in situ tumor-specific CD8 response in responders
LIVER METASTASES
Among patients with partial response, one patient who underwent resection of remaining liver metastases was monitored using single-cell RNA sequencing (scRNA-seq) and T cell receptor (TCR) sequencing. PBMCs were taken at baseline, at 1 month and at the time of liver surgery. Tumor-infiltrated lymphocytes (TILs) were is...
PMC10427431
Discussion
AtezoTRIBE, tumor, death, CRC, RAS-mutated, MSS, tumors
TUMOR, INFILTRATION, LIVER METASTASES, INFILTRATE, MUTANT, TUMORS
This study reports clinical and biological response with first-line chemo-immunotherapy for RAS-mutated metastatic CRC. This study reached its primary objective, with 3-month PFS of 90.7%, 6-month PFS of 60% and median PFS of 8.2 months, whereas the expected median PFS for such a population is 5–6 months with FOLFOX al...
PMC10427431
Methods
PMC10427431
Trial registration
The ‘Evaluation of the Safety and the Tolerability of Durvalumab Plus Tremelimumab Combined with FOLFOX in mCRC (MEDITREME)’ trial was prospectively registered with ClinicalTrials.gov identifier
PMC10427431
Inclusion and ethics
RAS-mutated
The protocol was approved by the Ethics Committee CPP TOURS – Région Centre – Ouest 1 on 27 March 2017 under the number 2017T1-03 and was registered with the French national health products agency (ANSM). The French ethical authorities asked us to include only RAS-mutated metastatic CRC because RAS WT patients must rec...
PMC10427431
Patient selection
Patients were enrolled in eight hospitals in France (Georges-François Leclerc Anticancer Center, UNICANCER, Dijon; Hôpital Franco-Britannique – Fondation Cognacq-Jay, Levallois-Perret; CHU, Nantes; CHU, Besançon; Clinique CARIO, Plérin; Saint Antoine, Hospital, Paris; Institut Bergonie, Bordeaux; and Pompidou Hospital,...
PMC10427431
Inclusion criteria
Reccurence, Cancer
ADVERSE EVENT, METASTASIS, LIVER METASTASES, ONCOLOGY, CANCER
Written informed consent and any locally required authorization obtained from the patient before performing any protocol-related procedures, including screening evaluationsMale or female age ≥18 years at time of study entryPerformance status of 0 or 1 according to the Eastern Cooperative Oncology Group and World Healt...
PMC10427431
Exclusion criteria
vitiligo, tumor, bleeding, malignancy, non-melanoma skin cancer, allergy, Crohn’s disease, psychiatric, autoimmune disease, toxicity, ischemia, psoriasis, hemoptysis, rest limb claudication or, comorbidity, gastritis, infection, hypotension, peptic ulcer disease, lentigo maligna, hypersensitivity, myocardial infarction...
VITILIGO, THIRD DEGREE HEART BLOCK, TUMOR, RECURRENCE, BLEEDING, CARDIOVASCULAR DISEASE, INFLAMMATORY BOWEL DISEASE, SYMPTOMATIC CONGESTIVE HEART FAILURE, ALLERGY, CARDIAC ARRHYTHMIA, LUNG METASTASES, CARCINOMA IN SITU, AUTOIMMUNE DISEASE, MOBITZ II, ISCHEMIA, PSORIASIS, GASTRITIS, BRAIN METASTASES, ULCERATIVE, INFECTI...
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study.Participation in another clinical study with an investigational product during the last 4 weeksAny previous treatment with a PD-1 or PD-L1/CTLA-4 inhibito...
PMC10427431
Study design and statistical hypothesis
colorectal MSI disease, colorectal MSS, MSS disease, colorectal MSS disease
DISEASE, SECONDARY
This was a multicenter, single-arm, open-label, phase 1/2 study. The study was performed in two steps (Extended Data Fig. The primary objective of step 2 was to determine efficacy of the combination of durvalumab (anti-PD-L1) + tremelimumab (anti-CTLA-4) + mFOLFOX6 in terms of PFS in patients with colorectal MSS diseas...
PMC10427431
Procedures
tumor, Tumor, Cancer
DISEASE PROGRESSION, TUMOR, TUMOR, DISEASE, BLOOD, CANCER
Patients received first-line induction with mFOLFOX6 consisting of an intravenous infusionClinical data were collected at the Department of Statistics of the Centre Georges-François Leclerc. Tumor assessments were based on investigator-reported measurements and were performed according to RECIST version 1.1 and repeate...
PMC10427431
Plasma collection
After the blood sampling was done at the different times described above, a heparin tube was used to isolate and bank the plasma. For this purpose, after collection, the heparin tube was centrifuged at 1,000
PMC10427431