title
stringlengths
1
1.19k
keywords
stringlengths
0
668
concept
stringlengths
0
909
paragraph
stringlengths
0
61.8k
PMID
stringlengths
10
11
Results
PMC10578185
General information
Cancer
CANCER
A total of 33 patients with ER+/HER2- MBC progressed on previous treatment of anastrozole or letrozole in the Guangxi Medical University Cancer Hospital were recruited between April 2017 and November 2019. Two cases who did not take apatinib and one who only underwent 3 days of treatment were excluded. Finally, 30 case...
PMC10578185
Toxic effects
ADVERSE EVENTS
The drug-related adverse events (AEs) are presented in
PMC10578185
Discussion
tumor, breast cancer
ADVERSE EVENTS, TUMOR, METASTASIS, BREAST CANCER
Endocrine therapy is a standard of care for ER+/HER2- MBC, and chemotherapy is the second approach. Unfortunately, resistance eventually develops in MBC and becomes a major clinical challenge. There is a need to find new therapeutic strategies to improve treatment outcomes. Angiogenesis promotes tumor invasion and meta...
PMC10578185
Limitations
Besides, there were several limitations in this study. First, only 30 eligible patients were included in our study, and the subgroup analysis relied on a small number of subjects, which would affect the accuracy of results. Besides, it was of great urgency to explore and unveil alternative treatment option for highly p...
PMC10578185
Author contribution
RECRUITMENT
Yongkui Lu conceived this study. Aihua Tan designed the study. Hongxue Wang, Li Nong, Yuxian Jia, Wuning Zhong, Fanghui Qin, Han Wang, Jing Tang were responsible for subject recruitment and data collection. Li Nong performed statistical analysis. Yan Liu oversaw the statistical analysis. Aihua Tan wrote the paper. Yong...
PMC10578185
Disclosure statement
No potential conflict of interest was reported by the authors.
PMC10578185
Data sharing statement
The data used and analyzed in the study is available from the corresponding author on reasonable request.
PMC10578185
Ethical statement
The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All of the enrolled patients or their family members signed the informed consent and could actively cooperate with the treatment. A...
PMC10578185
Reporting checklist
The authors have completed the TREND reporting checklist.
PMC10578185
References
PMC10578185
Subject terms
ADVERSE REACTIONS, INFLUENZA B, INFLUENZA A, SECONDARY, INFLUENZA
Despite vaccine availability, influenza remains a substantial global public health concern. Here, we report interim findings on the primary and secondary objectives of the safety, reactogenicity, and humoral immunogenicity of a quadrivalent messenger RNA (mRNA) vaccine against seasonal influenza, mRNA-1010, from the fi...
PMC10279702
Introduction
human illness, death, infectious, A/H1N1
INFLUENZA A, DISEASE, INFLUENZA
Vaccination remains an essential public health strategy for the prevention of influenzaFour types of influenza viruses exist: A, B, C, and D; however, only A and B are responsible for the majority of human illness, with influenza A the major cause of severe disease and death in older adultsGenerally, the overall effect...
PMC10279702
Results
PMC10279702
Participants
In Part 1 of the study, a total of 180 participants aged ≥18 years were randomly assigned to receive placebo or 1 dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) between July 6, 2021, and August 18, 2021 (Fig. 
PMC10279702
Participant disposition by study part.
infection
INFECTION, ADVERSE EVENT, CARDIAC ARREST, INFLUENZA
One participant in the mRNA-1010 100-µg group in Part 2 of the study died due to cardiac arrest. This adverse event was considered by the investigator as unrelated to the study vaccination. All randomly assigned participants who received study vaccination were included in the safety population; participants were includ...
PMC10279702
Safety
In Part 1 of the trial, any solicited local ARs within 7 days of mRNA-1010 vaccination were reported by 82.6%, 85.7%, and 91.3% of participants aged 18–49 years in the 50-µg, 100-µg, and 200-µg groups, respectively, and by 63.6%, 92.0%, and 90.5% of participants aged ≥50 years, respectively (Fig. 
PMC10279702
Immunogenicity
INFLUENZA
In Part 1 of the trial, all dose levels of mRNA-1010 (50 µg, 100 µg, and 200 µg) elicited immune responses in participants aged 18–49 years and ≥50 years against all vaccine-matched influenza strains at Day 29 (28 days after vaccination) as measured by HAI (Fig. 
PMC10279702
GMTs and GMFRs of anti-hemagglutinin antibodies for vaccine-matched seasonal influenza strains in adults in Part 1.
INFLUENZA A, INFLUENZA B
Hemagglutination inhibition GMTs with associated 95% CIs against seasonal influenza A strains (A/Wisconsin/588/2019[H1N1]pdm09 and A/Hong Kong/45/2019[H3N2]) or influenza B strains (B/Washington/02/2019 (B/Victoria lineage) and B/Phuket/3073/2013 (B/Yamagata lineage)) are shown at Day 1 (baseline) and Day 29 (28 days a...
PMC10279702
GMTs and GMFRs of anti-hemagglutinin antibodies for vaccine-matched seasonal influenza strains in adults in Part 2.
INFLUENZA A, INFLUENZA B
Hemagglutination inhibition GMTs with associated 95% CIs against seasonal influenza A strains (A/Wisconsin/588/2019[H1N1]pdm09 and A/Cambodia/e0826360/2020[H3N2]) or influenza B strains (B/Washington/02/2019 (B/Victoria lineage) and B/Phuket/3073/2013 (B/Yamagata lineage)) are shown at Day 1 (baseline) and Day 29 (28 d...
PMC10279702
Ratios of GMTs of anti-hemagglutinin antibodies after vaccination with mRNA-1010 compared with Afluria in adults in Part 2.
INFLUENZA
Ratios of HAI GMTs with associated 95% CIs against vaccine-matched seasonal influenza strains (A/Wisconsin/588/2019[H1N1]pdm09, A/Cambodia/e0826360/2020[H3N2], B/Washington/02/2019 (B/Victoria lineage), and B/Phuket/3073/2013 (B/Yamagata lineage)) at 28 days after vaccination with mRNA-1010 compared with Afluria are sh...
PMC10279702
Discussion
deaths
INFLUENZA A, EVENTS, INFLUENZA B, INFLUENZA
This manuscript presents interim analysis findings from 2 parts of a phase 1/2, first-in-human clinical trial on the safety and immunogenicity of an investigational mRNA-based quadrivalent vaccine against seasonal influenza (mRNA-1010) in healthy adults ≥18 years. The placebo-controlled Part 1 of this study showed that...
PMC10279702
Methods
PMC10279702
Trial design and participants
chronic diseases
CHRONIC DISEASES, INFLUENZA
This is a first-in-human, phase 1/2, randomized, observer-blinded study at 20 sites in the United States to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1010 in adults ≥18 years of age (NCT04956575). The study comprises 3 parts, which assessed mRNA-1010 or placebo in healthy adults in Part 1, followe...
PMC10279702
Vaccines
STERILE, VIRUS, INFLUENZA
In Part 1, participants received mRNA-1010 or placebo (normal saline), while in Part 2, participants received mRNA-1010 or a licensed standard dose quadrivalent influenza vaccine (Afluria). mRNA-1010 includes mRNAs encoding for the surface glycoprotein HA of four influenza virus strains formulated in lipid nanoparticle...
PMC10279702
Objectives
INFLUENZA A, SECONDARY
The primary objectives of Part 1 were to evaluate the safety and reactogenicity of a single dose of mRNA-1010 (50 µg, 100 µg, and 200 µg) versus placebo and to evaluate the humoral immunogenicity of a single dose of mRNA-1010 against vaccine-matched influenza A and B strains at Day 29. The objectives of Part 2 were to ...
PMC10279702
Safety assessments
swelling/tenderness, myalgia, fatigue, fever, pain, headache, chills, arthralgia
ADVERSE REACTIONS, ADVERSE EVENTS
Safety endpoints included solicited local and systemic adverse reactions (ARs) for 7 days after vaccination, safety laboratory abnormalities (Part 1 only), unsolicited adverse events (AEs) for 28 days after vaccination, as well as serious AEs (SAEs), AEs of special interest (AESIs), and medically attended AEs (MAAEs) t...
PMC10279702
Immunogenicity assessments
BLOOD, INFLUENZA A
Blood samples for immunogenicity assessments were collected on Days 1 (baseline), 8 (Part 1 only), 29, and 181 (end of study). This report summarizes immunogenicity assessments at baseline and Day 29. Immunogenicity endpoints included geometric mean titers (GMTs) at Day 1 and 29, geometric mean fold rises (GMFRs) at Da...
PMC10279702
Statistical analyses
infection
EVENTS, INFECTION, INFLUENZA
This phase 1/2 study did not test any formal statistical hypotheses. Sample size (described in the Supplementary Methods) was considered sufficient to provide a descriptive summary of the safety and immunogenicity of different dose levels of mRNA-1010. All safety assessments except for solicited local and systemic ARs ...
PMC10279702
Reporting summary
Further information on research design is available in the 
PMC10279702
Supplementary information
The online version contains supplementary material available at 10.1038/s41467-023-39376-7.
PMC10279702
Acknowledgements
We thank the participants for their dedication and contributions to the study, the Study Investigators, and our clinical team colleagues at PPD for their collaboration. Medical writing and editorial assistance were provided by Emily Stackpole, PhD, and Jared MacKenzie, PhD, of MEDiSTRAVA in accordance with Good Publica...
PMC10279702
Author contributions
C.H.
I.L., R.N., L.C., K.S., D.S., C.H., W.H., D.R.S., J.A., and R.P. contributed to the study concept and design. Data were collected by DE and HS, then analyzed and interpreted by I.L., R.N., D.E., H.S., A.A., R.C., W.H., D.R.S., J.A., and R.P. All authors contributed to the drafting and critical review of this manuscript...
PMC10279702
Peer review
PMC10279702
Data availability
Access to patient-level data presented in this article (antibody assays, safety, and reactogenicity) and supporting clinical documents with external researchers who provide methodologically sound scientific proposals will be available upon reasonable request and subject to review from 2 years after study completion. Su...
PMC10279702
Competing interests
C.H.
I.L., R.N., L.C., K.S., A.A., D.S., C.H., R.C., W.H., D.R.S., J.A., and R.P. are employees of and shareholders in Moderna, Inc. D.E. and H.S. declare no competing interests.
PMC10279702
References
PMC10279702
Background
stress-related disorders
DISORDER, DISEASE, DISORDERS
Stress-related mental health disorders have steadily increased and contributed to a worldwide disease burden with up to 50% experiencing a stress-related mental health disorder worldwide. Data suggest that only approximately 20%-65% of individuals receive treatment. This gap in receiving treatment may be attributed to ...
PMC10612013
Objective
This study examined if app-based guided mindfulness could improve subjective levels of stress and influence physiological markers of stress reactivity in a population with elevated symptoms of stress.
PMC10612013
Methods
PHYSIOLOGICAL STRESS, COLD, HEART
The study included 163 participants who had moderate to high perceived stress as assessed by the Perceived Stress Scale (PSS-10). Participants were randomly allocated to 1 of 5 groups: a digital guided program designed to alleviate stress (Managing Stress), a digital mindfulness fundamentals course (Basics), digitally ...
PMC10612013
Results
The results showed that PSS-10 and Pittsburgh Sleep Quality Index scores for the Managing Stress (all
PMC10612013
Conclusions
These results demonstrate efficacy of app-based mindfulness in a population with moderate to high stress on improving self-reported stress, sleep quality, and physiological measures of stress during an acute stress manipulation task.
PMC10612013
Trial Registration
ClinicalTrials.gov NCT05832632; https://www.clinicaltrials.gov/ct2/show/NCT05832632
PMC10612013
Introduction
PMC10612013
Background
cognitive functioning
Elevated stress is a state in which an individual experiences excessive or prolonged psychological and physiological strain [Mindfulness is defined as a state of being attentive to and bringing awareness to sensations that are taking place in the present moment without judgment [However, the MBSR program is time consum...
PMC10612013
Effects of Mindfulness on Physiological Stress Reactivity
DYSFUNCTION
In addition to its psychological and cognitive effects, mindfulness has been found to have physiological effects that reduce stress. Regular mindfulness practice has been associated with decreased blood pressure, increased heart rate variability (HRV), and reduced cortisol levels [Elevated stress is widely regarded as ...
PMC10612013
Effects of Mindfulness on Acute Stress
PHYSIOLOGICAL STRESS, COLD
The cold pressor task (CPT) is a laboratory test commonly used to induce a physiological stress response in participants. The CPT involves immersing the participant's hand in an ice-cold water bath for 3 minutes, which causes vasoconstriction in the submerged hand. This triggers a physiological response, which activate...
PMC10612013
Aims of the Study
PHYSIOLOGICAL STRESS
This study examined if 3 different formats of digital mindfulness interventions demonstrated efficacy in terms of reducing self-reported levels of stress, sleep quality, and influencing physiological markers of stress reactivity in a population with elevated levels of stress.To accomplish the experimental aim, particip...
PMC10612013
Methods
PMC10612013
Ethical Considerations
The participants were recruited through flyers and advertisements at a local university (University of Southern Denmark) and the Region of Southern Denmark. All procedures were conducted in accordance with the local ethical committee (
PMC10612013
Experimental Procedures
RECRUITMENT, COLD
The study included 5 experimental groups using a pre-post design.Overall, 48 hours prior to the laboratory visit, eligible participants were emailed instructions to refrain from alcohol and nicotine before coming to the laboratory to avoid known influences of these factors on autonomic activity [Upon arrival for the fi...
PMC10612013
Psychological Measures and Physiological Measures
The experimental methods and outcome measures are described in detail in the
PMC10612013
Interventions
The interventions were completed using a custom-built research smartphone app. Participants were given access to a smartphone app that was built for the purpose of conducting scientific research at the University of Southern Denmark that contained the training content for each specific intervention. The app has been ap...
PMC10612013
Managing Stress (Mindfulness) Intervention
The content of the training was provided by Headspace [
PMC10612013
Basics (Mindfulness) Intervention
The content of the training was provided by Headspace [
PMC10612013
Breathing (Mindfulness) Intervention
The content of the training was provided by Headspace [
PMC10612013
Audiobook Intervention
Mindfulness has been hypothesized to train attention and affect through interoceptive nonjudgmental awareness [
PMC10612013
Waitlist Control
The Waitlist Control group required that participants did not follow an intervention. However, the Waitlist Control group was given the option to obtain access to 1 of the 3 active interventions after completion of the study.
PMC10612013
Statistical Analysis
SD, η²p
All data are presented as mean ± 1 SD unless otherwise stated. Assumptions of statistical tests for normal distribution and sphericity of data were checked. A series of mixed groups (Managing Stress, Basics, Breathing, Audiobook, Waitlist control) × time (pretest, posttest) ANOVAs were performed on PSS-10, PSQI, MAAS, ...
PMC10612013
Results
PMC10612013
Psychological Measures: PSS-10, PSQI, MAAS, and CPT Self-Reported Stress
There was an interaction for PSS-10 across the 5 groups and time (PSS-10 results pre and post across the 5 groups. $: interaction effect; #: simple main effects of time (follow-ups). PSS-10: Perceived Stress Scale.There was an interaction for PSQI across the 5 groups and time (There was no significant interaction (No i...
PMC10612013
Discussion
PMC10612013
Principal Findings
depression, Stress, anxiety
PHYSIOLOGICAL STRESS, DISORDERS
This study sought to investigate if 3 formats of digital mindfulness interventions would show efficacy in reducing subjective and physiological levels of stress in a population with elevated symptoms of stress. The study found that self-reported stress as measured by PSS-10 was significantly reduced in the Managing Str...
PMC10612013
Self-Reported Effects of Stress and Sleep Quality
insomnia
The magnitude of change for the PSS-10 was larger in the Managing Stress group and the Basics groups compared to the Breathing and control groups, thus finding partial support for hypothesis 1 (H1). Our findings expand upon the results of previous studies that found digital mindfulness interventions improved stress amo...
PMC10612013
Physiological Effects of Stress
pain
We did not find significant group differences in subjective levels of stress after administration of the CPT from the preintervention to the postintervention period. However, we did observe significant differences in HRV activity both in the expectation phase before the CPT, during the CPT, and in the recovery period a...
PMC10612013
Strengths and Limitations
Although the results of this study are promising regarding the efficacy in 2 of the 3 app-based mindfulness interventions, several limitations must be noted. First, the sample primarily comprised young university students in their twenties, thus the generalizability of our findings may be limited. Second, this study di...
PMC10612013
Conclusions
WS
In summary, our findings extend previous studies suggesting the efficacy of Headspace’s app-based mindfulness interventions, specifically the Managing Stress and Basics content, to reduce stress in populations with elevated stress levels. Specifically, we found stress-buffering effects in a relatively diverse sample of...
PMC10612013
Abbreviations
autonomic nervous systemcold pressor taskheart rate variabilityMindful Attention Awareness Scalemindfulness-based stress reductionparasympathetic nervous systemPittsburgh Sleep Quality IndexPerceived Stress Scalesympathetic nervous system
PMC10612013
Data Availability
The data sets generated or analyzed during the study are available from the corresponding author upon request.
PMC10612013
Background
RECURRENCE
Although complete mesocolic excision (CME) is supposed to be associated with a higher lymph node (LN) yield, decreased local recurrence, and survival improvement, its implementation currently is debated because the evidence level of these data is rather low and still not supported by randomized controlled trials.
PMC10838239
Method
SECONDARY, PERIOPERATIVE COMPLICATION
This is a multicenter, randomized, superiority trial (NCT04871399). The 3-year disease-free survival (DFS) was the primary end point of the study. The secondary end points were safety (duration of operation, perioperative complications, hospital length of stay), oncologic outcomes (number of LNs retrieved, 3- and 5-yea...
PMC10838239
Results
Interim data analysis is presented in this report. The study enrolled 258 patients in nine referral centers. The number of LNs retrieved was significantly higher after CME (25 vs. 20;
PMC10838239
Supplementary Information
The online version contains supplementary material available at 10.1245/s10434-023-14664-0.
PMC10838239
Keywords
tumor
DISEASE, TUMOR, COLORECTAL CANCER, POSTOPERATIVE COMPLICATIONS
Open access funding provided by Università degli Studi di Torino within the CRUI-CARE Agreement.Colorectal cancer (CC) is the third most common tumor worldwide and ranks second in terms of death-related cancer/year. Actually, the standard of care is surgery, with 5-year survival rates of 80% or higher for all stages to...
PMC10838239
Methods
PMC10838239
Study Design
tumors
ONCOLOGY, METASTASIS, TUMORS
The current study is a randomized, superiority, two-arm, interventional trial involving nine Italian referral centers from the Italian Society of Surgical Oncology (SICO). All consecutive patients with RSCC located between the cecum and proximal third of the transverse colon without distant metastasis were eligible for...
PMC10838239
Randomization and Blinding
Patients were enrolled in the trial by each participating surgeon after signing the informed consent agreement. The study was a single-blind trial, with only the patients blinded to the surgical procedure.The coordinating center was responsible for patient allocation (CME or non-CME). The randomization list was managed...
PMC10838239
Interventions and Quality Control
METASTASES
The types of surgical interventions are detailed in the previously published study protocol.Furthermore, every surgical specimen was carefully measured according to promotor center indications to assess its quality according with Benz classification.Two types of protocol deviation were recognized: “contamination” for n...
PMC10838239
Statistical Analysis
The descriptive statistics are reported by the intervention arm summarizing the continuous data as a median with the interquartile range (IQR). Categorical data are reported as absolute frequencies and percentages. Wilcoxon-type tests were performed for continuous variables and the Pearson chi-square test or Fisher’s e...
PMC10838239
Interim Analysis
The interim analysis for the interim futility assessment was reported 12 months after the beginning of the study. Based on the results of this interim assessment, the study was stopped if no significant interim increase in LN yield was documented in the experimental arm.
PMC10838239
Secondary Outcomes
REGRESSION
Univariable logistic regression model estimates for the binary end points and linear regression model estimates for continuous ones were performed by considering the intervention as a covariate. Gamma regression models were considered for positive-skew end points. The model results are reported as odds ratios (ORs) wit...
PMC10838239
Sample Size Calculation
Details of sample size calculation are available in the study protocol.
PMC10838239
Role of the Funding Source
The funding source for this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
PMC10838239
Discussion
vascular injuries, tumor, early-stage disease
SYSTEMIC DISEASE, RECURRENCE, TUMOR, METASTASIS, POSTOPERATIVE COMPLICATIONS, POSTOPERATIVE COMPLICATION, MINOR, POSTOPERATIVE COMPLICATION, WEST, RECTAL CANCER
As a new technique, CME remains under investigation. Although renewed attention to meticulous surgical technique certainly has its merits, routine implementation of CME seems currently unfounded for several reasons. First, in contrast to rectal cancer, local recurrence originating from an incomplete or non-optimal remo...
PMC10838239
Acknowledgment
This study was supported by the University of Turin Local Research funding SOLM_RILO_18_01.
PMC10838239
Funding
Open access funding provided by Università degli Studi di Torino within the CRUI-CARE Agreement.
PMC10838239
Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10838239
DISCLOSURE
There are no conflicts of interest.
PMC10838239
References
PMC10838239
Key words
±
SECONDARY
The objective of the present study was to evaluate the efficacy of oral administration of vitamin D supplementation in reducing BMI and lipid profile in adolescents and young adults from a cohort in Bucaramanga, Colombia. One hundred and one young adults were randomly assigned to one of two doses of vitamin D [1000 int...
PMC9947753
Introduction
diabetesVitamin D deficiency, stroke, obesity
OBESITY, CARDIOVASCULAR DISEASE, STROKE, CHRONIC DISEASES, VITAMIN D DEFICIENCY, VITAMIN D DEFICIENCY, DYSLIPIDEMIA
Vitamin D deficiency constitutes a worldwide public health problem. It is highly prevalent even in countries such as Colombia with a hot tropical climateSerum vitamin D deficiency has been associated with several chronic diseases, including cardiovascular disease, stroke and diabetesVitamin D deficiency has also been a...
PMC9947753
Materials and methods
PMC9947753
Design
NCT04377386
A triple-blind parallel two-arm randomised controlled clinical trial. The study participants were young adults from the SIMBA cohort, which began in 2006 with 1282 children between 6 and 10 years of age in the city of Bucaramanga, Colombia (latitude: 7⋅12539)Follow-up of the participants throughout the intervention.The...
PMC9947753
Intervention
’ adverse
DEFICIENCY
The intervention group received 1000 IU of vitamin D and the control group 200 IU of vitamin D daily for 15 weeks. All participants were given 105 doses of vitamin D in white containers identical in terms of organoleptic characteristics to ensure that both participants and researchers were blinded to treatment. The sup...
PMC9947753
Sample size
overweight, obesity
It was calculated taking into account an expected difference in the results of the study (overweight, obesity and altered lipid profile) of 20 %
PMC9947753
Outcomes
SECONDARY
The primary outcomes were serum 25(OH)D levels, BMI and lipid profile. The secondary were waist-hip ratio, skinfolds and fasting blood glucose.
PMC9947753
Statistical methods
An intention-to-treat analysis was performed. The description of the categorical variables was made using absolute and relative values; of the quantitative variables that presented a normal distribution in the Shapiro–Wilk test the mean and standard deviation were reported, otherwise, the median and interquartile range...
PMC9947753
Ethical considerations
This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects/patients were approved by the Research Ethics Committee of the Fundación Cardiovascular de Colombia (Record No. 480 of July 16, 2019). Written informed consent was obtained from all ...
PMC9947753
Results
The potentially eligible population sample was 494 adolescents and young adults (
PMC9947753
Baseline characteristics of study participants
The average age of the participants was 22⋅6 [±1⋅5] years, 56⋅44 % were women, with a median BMI of 23⋅3 [Q1: 20⋅8; Q3: 26⋅8]. Median baseline serum vitamin D [25(OH)D] levels for the 1000 IU group were 23⋅3 ng/ml [Q1: 20⋅2; Q3: 31⋅3], and for the 200 IU of 24⋅7 ng/ml [Q1: 21⋅6; Q3: 31⋅6]. No differences were found bet...
PMC9947753