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Detection and quantification of blastocystis by specific real-time quantitative PCR
A real-time quantitative PCR assay with a specific probe for
PMC10636941
Subtyping of blastocystis by massively parallel amplicon sequencing
Samples positive for
PMC10636941
Parasitome survey using massively parallel amplicon profiling of the 18S rDNA gene
The parasitome survey was performed using massively parallel sequencing with five different PCR amplicons of the 18S rDNA gene, as reported in detail previously [
PMC10636941
Quantification of
The single-cell protists with a signal in the parasitome survey (
PMC10636941
Bacteriome analysis
The processing, DNA library preparation and sequencing had been done previously by massively parallel amplicon sequencing of the V3-V4 region of the bacterial 16S rRNA gene [
PMC10636941
Statistical analysis
The prevalence of single-cell protists was determined by counting any PCR positivity at any level. Their presence and quantity were then modeled using generalized estimating equations (GEE) with the subject as the grouping variable, time point (factor with three levels—0, 3 and 6 months) and a first-order autoregressiv...
PMC10636941
Results
PMC10636941
Fecal parasitome analysis
The molecular survey using 18S rDNA parasitome profiling and/or specific quantitative PCR for the single-cell protists revealed positivity in widely varying quantities: in The subject-wise prevalence of these three protists, calculated as at least once positive among the three time points, was highest in Sample- and su...
PMC10636941
Blastocystis subtypes
Blastocystis
Of 26 Blastocystis subtypes. (
PMC10636941
Protists and the fecal bacteriome
The presence of Alpha diversity of the faecal bacteriome and associations with positivity for Redundancy analysis performed on Hellinger-transformed bacterial abundance data indicated no effect of the intervention (When studying the bacterial taxa associated with positivity for parasites using adjusted GEE (Table Bacte...
PMC10636941
Discussion
CDA
This study analyzed the single-cell parasitome in a randomized clinical trial of probiotic strain intervention in CDA and found a relatively stable protist colonization (By targeted molecular testing using quantitative real-time PCR, we first looked at the prevalence of The prevalence of Although The colonization by th...
PMC10636941
Strengths and limitations
celiac disease
CELIAC DISEASE
Our study provides a unique insight into a novel topic in celiac disease research as no study has yet investigated the gut parasitome by molecular techniques. The samples were taken longitudinally, which helps decrease the effects of short-term fluctuations in the abundance of individual microbial taxa [The main limita...
PMC10636941
Conclusions
The prevalence of
PMC10636941
Acknowledgements
Zuzana Lhotská from the Institute of Parasitology, Biology Centre, Czech Academy of Sciences, and Zdeněk Verner, from Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec (BIOCEV), are sincerely thanked for preparing cultures of
PMC10636941
Author contributions
RECRUITMENT
JH performed laboratory analyses, analysed some of the data and wrote the manuscript; EO performed some laboratory analyses; AH supervised the laboratory analyses and co-lead the study; KJM and MJ contributed to the preparation of the detection assays, construction of quantitative calibrators and manuscript revision; C...
PMC10636941
Funding
Celiac Disease
CELIAC DISEASE
Open access funding provided by Lund University. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 874864 HEDIMED. This publication reflects only the authors' views, and the European Commission is not responsible for any use that may be m...
PMC10636941
Availability of data and materials
Data are available upon reasonable request.
PMC10636941
Declarations
PMC10636941
Ethics approval and consent to participate
The study was approved by the Ethics Committee of the Medical Faculty, Lund University, on September 8th, 2011 (Dnr 2011/335) and on September 1st, 2021 (Dnr 2021-04470). The study is registered in ClinicalTrials.gov (NCT03176095).
PMC10636941
Consent for publication
Not applicable.
PMC10636941
Competing interests
MINOR
DA is an inventor in a patent application based on the results of the clinical trial but has signed over all legal rights to the patent to Probi AB. Probi AB has developed and supplied the study material (active and placebo products) for the trial as well as financially supported the trial with minor costs for analyzin...
PMC10636941
References
PMC10636941
Purpose:
P.
K. Fanucci and M.J. Pilat contributed as co-first authors and A. Omuro and P. LoRusso as co-last authors to this article.Prior presentation: This study was presented at ASCO 2022 Abstract #367158.Isocitrate dehydrogenase (
PMC10035510
Methods:
Patients with recurrent, contrast-enhancing
PMC10035510
Results:
astrocytoma
ASTROCYTOMA
A total of 15 evaluable patients were enrolled. Histology was astrocytoma (
PMC10035510
Conclusion:
tumors, SD
TUMORS
The study did not meet the prespecified response-based activity threshold for moving to step 2. However, prolonged SD was observed in patients with grades 2 and 3 histologies, suggesting olaparib monotherapy could be of clinical benefit in select populations. Grade 4 tumors per 2021 World Health Organization classifica...
PMC10035510
Significance:
A single-arm phase II trial of olaparib in
PMC10035510
Introduction
heterogenous, Gliomas, tumor, primary brain tumors, gliomas
GLIOMAS, TUMOR, PRIMARY BRAIN TUMORS, DISEASES, GLIOMAS
Gliomas represent a heterogenous group of diseases that account for most primary brain tumors (In general, first-line treatment for gliomas includes maximal safe resection which is often limited by tumor extent and location, adjuvant radiation, and alkylator-based chemotherapy. Chemotherapy options include temozolomide...
PMC10035510
Materials and Methods
PMC10035510
Patient Selection
glioma
GLIOMA
Eligible patients had recurrent or transformed glioma that progressed despite standard therapy or for which no effective standard therapy existed with evidence of an
PMC10035510
Study Treatment and Design
Toxicities
ADVERSE EVENT
The primary objective of this trial was to estimate the overall response rate (ORR) of olaparib in patients with Treatment cycles were 28 days. Patients were administered olaparib in tablet form orally 300 mg twice daily continually, irrespective of food intake. No premedications were required. Toxicities were graded u...
PMC10035510
Statistical Methods
PD
DISEASE, SECONDARY
The power analysis and sample size estimation were completed using the Bayesian adaptive trial design method. We modeled the probability of ORR using Beta distributions. The prior distribution is Beta(0.1, 0.9), which is fairly pessimistic; the expected value is 0.1, reflecting the response rate based on previous exper...
PMC10035510
Data Availability
The data generated in this study are available upon request from the corresponding author.
PMC10035510
Results
PMC10035510
Patient Demographics
toxicity, tumor, CNL
TUMOR
Sixteen patients were enrolled. Fifteen patients were evaluable for response and toxicity. One patient was found to be ineligible after signing consent (Consort diagram.Demographics and baseline characteristics (Summary of patients’ diagnosis and tumor characteristicsAbbreviations: CNL, copy-number loss; LOF, loss of f...
PMC10035510
Toxicity
toxicities, nausea, fatigue
ADVERSE EVENTS
There were no unexpected toxicities reported and most toxicities were grade 1 or 2. The most common toxicities were nausea (67%) and fatigue (47%; Most common (>10%) treatment-related and grade 1–3 treatment-related adverse events (maximum grade, all cycles;
PMC10035510
Efficacy
PD, death, tumor
DISEASE, TUMOR
All 15 patients were evaluable for response (Patients’ response to olaparibNOTE: PFS defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. OS calculated from initiation of treatment to date of death or last known date of contact. + = alive or lost to follow-up....
PMC10035510
Discussion
tumor, tumors, infiltrative disease
GLIOBLASTOMA, TUMOR, TUMORS
Olaparib monotherapy was well tolerated in patients with recurrent or progressive contrast-enhancing PARP is important in the repair of single-strand breaks (Recently, preliminary results of the OLAGLI trial investigating olaparib in 35 patients with recurrent An important concern in the development of novel therapies ...
PMC10035510
Supplementary Material
Tumor
PROGRESSION, TUMOR
Definition of Progression, Tumor Classification, and Eligibility Criteria, retreatment criteriaClick here for additional data file.Representativeness of Study ParticipantsClick here for additional data file.
PMC10035510
Acknowledgments
P.
The authors would like to thank CTEP, The Catherine Ivy Foundation, and The Rising Tide Foundation for their support of this project through grants to P. LoRusso.
PMC10035510
Authors’ Disclosures
Durecki, P.
EMD
Y. Shyr reports grants from NIH/NCI during the conduct of the study; grants from NIH outside the submitted work. S. Boerner reports grants from NCI-CTEP and Rising Tide Foundation during the conduct of the study. D. Durecki reports grants from NIH/NCI UM1CA186689 during the conduct of the study. J. Drappatz reports oth...
PMC10035510
Authors’ Contributions
PMC10035510
References
PMC10035510
Key Points
PMC10346121
Question
nonsuicidal self-injury
What are the efficacy and mechanisms of change of a therapist-guided, internet-delivered emotion regulation therapy for nonsuicidal self-injury among adolescents?
PMC10346121
Findings
assessor-rated nonsuicidal self-injury, nonsuicidal self-injury
In this randomized clinical trial that included 166 adolescents, internet-delivered emotion regulation individual therapy delivered adjunctive to treatment as usual resulted in an 82% reduction in masked assessor-rated nonsuicidal self-injury frequency (vs a 47% reduction in treatment as usual only), a statistically si...
PMC10346121
Meaning
nonsuicidal self-injury
A therapist-guided emotion regulation treatment delivered online may overcome common treatment barriers and increase availability of evidence-based psychological treatments for adolescents with nonsuicidal self-injury.This randomized clinical trial examines the effectiveness of internet-delivered emotion regulation ind...
PMC10346121
Importance
Nonsuicidal self-injury
Nonsuicidal self-injury is prevalent in adolescence and associated with adverse clinical outcomes. Effective interventions that are brief, transportable, and scalable are lacking.
PMC10346121
Objective
nonsuicidal self-injury
To test the hypotheses that an internet-delivered emotion regulation individual therapy for adolescents delivered adjunctive to treatment as usual is superior to treatment as usual only in reducing nonsuicidal self-injury and that improvements in emotion regulation mediate these treatment effects.
PMC10346121
Design, Setting, and Participants
nonsuicidal self-injury disorder
This 3-site, single-masked, randomized superiority trial enrolled participants from November 20, 2017, to April 9, 2020. Eligible participants were aged between 13 and 17 years and met diagnostic criteria for nonsuicidal self-injury disorder; they were enrolled as a mixed cohort of consecutive patients and volunteers. ...
PMC10346121
Interventions
Twelve weeks of therapist-guided, internet-delivered emotion regulation individual therapy delivered adjunctive to treatment as usual vs treatment as usual only.
PMC10346121
Main Outcomes and Measures
Primary outcome was the youth version of the Deliberate Self-harm Inventory, both self-reported by participants prior to treatment, once every week during treatment, and for 4 weeks posttreatment, and clinician-rated by masked assessors prior to treatment and at 1 and 3 months posttreatment.
PMC10346121
Results
self-injury, nonsuicidal self-injury
A total of 166 adolescents (mean [SD] age, 15.0 [1.2] years; 154 [92.8%] female) were randomized to internet-delivered emotion regulation therapy plus treatment as usual (84 participants) or treatment as usual only (82 participants). The experimental intervention was superior to the control condition in reducing clinic...
PMC10346121
Conclusions and Relevance
self-injury, nonsuicidal self-injury
In this randomized clinical trial, a 12-week, therapist-guided, internet-delivered emotion regulation therapy delivered adjunctive to treatment as usual was efficacious in reducing self-injury, and mediation analysis supported the theorized role of emotion regulation as the mechanism of change in this treatment. This t...
PMC10346121
Trial Registration
ClinicalTrials.gov Identifier:
PMC10346121
Introduction
NSSI, Nonsuicidal self-injury, psychiatric, assessor-rated NSSI, impulsive self-destructive behaviors
SECONDARY
Nonsuicidal self-injury (NSSI), the deliberate destruction of one’s body tissue without suicidal intent,There are very few empirically supported treatments for NSSI in adolescence.One way to treat NSSI more effectively is to target key mechanisms underlying NSSI.This study presents the results from what is to our knowl...
PMC10346121
Methods
PMC10346121
Design
RECRUITMENT
This was a 3-site, single-masked, randomized superiority trial comparing a 12-week, therapist-guided IERITA delivered adjunctive to TAU with TAU only for adolescents with NSSID and their parents. The trial was conducted within the Child and Adolescent Mental Health Services (CAMHS) in Stockholm, Västra Götaland, and Sk...
PMC10346121
Participants
NSSI, anorexia nervosa, psychotic or bipolar I disorder, primary psychiatric disorder
DISORDER
Referrals from health care professionals and self-referrals from families living in Sweden were accepted. The trial was advertised in CAMHS, schools, and newspapers and on social media.Inclusion criteria for the adolescents were: ages 13 to 17 years, meeting diagnostic criteria for NSSID, experiencing 1 or more NSSI ep...
PMC10346121
Procedures
psychiatric disorders
Procedures for being admitted into the trial included an initial telephone screening, consecutive self-reported baseline assessments every 7 days for 4 weeks, and a face-to-face assessment at the clinic. During the face-to-face assessment, a psychologist or psychotherapist administered semi-structured interviews to ass...
PMC10346121
Outcomes
NSSI
The primary outcome was self-reported and clinician-rated NSSI frequency as measured by the youth version of the Deliberate Self Harm Inventory (DSHI-Y).
PMC10346121
Interventions
The therapist-guided IERITA used in this study had been optimized based on feasibility studies,The comparison condition TAU was chosen to control for some nonspecific aspects of treatment (eg, time, monitoring) and ensure patient safety. The TAU was delivered in both conditions within regular CAMHS care by community cl...
PMC10346121
Statistical Analysis
DERS-16, NSSI, self-destructive behaviors, assessor-rated NSSI
REGRESSION
See eMethods in Treatment effects were evaluated according to the intention-to-treat principle. The primary outcome analysis of self-reported NSSI included treatment condition and weekly self-reports of NSSI frequency (using the DSHI-Y). A zero-inflated negative binomial generalized linear-mixed effects regression mode...
PMC10346121
Results
A total of 166 participants (mean [SD] age, 15.0 [1.2] years; 154 [92.8%] female) were recruited and randomly allocated to IERITA plus TAU (84 participants) or TAU only (82 participants) (
PMC10346121
Study and Participant Characteristics
Dysmorphic Disorder, borderline personality disorder, nonsuicidal self-injury, attention-deficit hyperactivity disorder, ADHD, BPD, dysmorphic disorder, hyperactive-impulsive, OCD, obsessive-compulsive disorder, Mini-International Neuropsychiatric
ANOREXIA NERVOSA AND BULIMIA
Abbreviations: ADHD, attention-deficit hyperactivity disorder; BDD, body dysmorphic disorder; BPD, borderline personality disorder; CBT, cognitive behavioral therapy; IERITA, internet-delivered emotion regulation individual therapy for adolescents; TAU, enhanced treatment as usual; NSSI, nonsuicidal self-injury; OCD, o...
PMC10346121
Characteristics of Enhanced Treatment as Usual Within Each Condition and Differences Between Conditions
SE, NSSI
Abbreviations: CBT, cognitive behavioral therapy; IERITA, internet-delivered emotion regulation therapy for adolescents; TAU, enhanced treatment as usual; SSRI, serotonin reuptake inhibitors.Description of the level and content of enhanced treatment as usual that both conditions received during the trial.Classes of psy...
PMC10346121
Results From the Generalized and Linear Mixed Model Analyses and Effect Sizes
SE, assessor-rated NSSI, NSSI
REGRESSION, SECONDARY, ADVERSE EVENTS, POSITIVE
Abbreviations: BSL, Borderline Symptom List; CGAS, Children’s Global Assessment Scale; Of count and continuous outcomes evaluating treatment differences in change from pretreatment to 1-month posttreatment (primary end point) and 3-month posttreatment (secondary end point). Fixed-effects parameter estimates β (SE) repr...
PMC10346121
Discussion
anxiety, NSSI, assessor-rated, psychiatric, depression
Findings of this randomized clinical trial support the efficacy of this IERITA delivered adjunctive to TAU (vs TAU only). IERITA resulted in greater improvements in NSSI frequency (both self-reported and assessor-rated) and emotion dysregulation from pretreatment to 1-month posttreatment than TAU only. Results also rev...
PMC10346121
Strengths and Limitations
NSSI
This study had several strengths. These include the use of TAU as the control condition, the use of weekly measures of NSSI, inclusion of both self-reported and clinician-administered assessments, integrity of the masked assessments, and the sexual orientation diversity of the sample.The study also has limitations. IER...
PMC10346121
Conclusions
NSSI
Results of this trial suggest that a 12-week, therapist-guided, IERITA delivered adjunctive to TAU is efficacious in the treatment of NSSI and related factors compared with TAU only. Findings that week-to-week improvements in emotion dysregulation were associated with week-to-week reductions in NSSI frequency during IE...
PMC10346121
Introduction
psychomotor disturbances, OGM, non-dysphoric, pain, mindfulness-based stress reduction, dysphoric, depression, Depression
EVENT
Depression is characterised by somatic symptoms such as poor sleep, low energy, and psychomotor disturbances [A key mechanism that is linked to OGM is rumination [Remoteness of memories (the age of the memory’s event) has been suggested to influence several characteristics of AM and therefore an important question is w...
PMC10306223
Outline of proposed mechanisms by which features of AM retrieval come to be compromised.
depression, depressed, OGM
POSITIVE
Rumination about self-relevant, semantically related information, and self-discrepant thinking are proposed to compromise the search for a specific memory and influence the remoteness, valence, and vantage perspective of the memory. Difficulty recalling specific memories, biases for retrieving more remote memories, usi...
PMC10306223
Methods
PMC10306223
Group demographic, diagnostic, and intervention compliance data.
depression, Depression
Diagnoses were assessed via the MINI-Plus [Participants aged 18–45 were recruited via university communications where individuals with a previous experience of depression were invited to participate in a study that involved either a meditation or colouring practice for four weeks. Participants were included in the stud...
PMC10306223
Measures
At baseline, the first six participants completed all questionnaires in writing, while the AMT was administered via Microsoft Excel [
PMC10306223
MINI-Plus structured interview
The MINI-Plus [
PMC10306223
Depression, Anxiety, Stress Scales (DASS)
The DASS [
PMC10306223
Rumination Response Scale (RRS)
The RRS [
PMC10306223
Self-Compassion Scale (SCS)
The SCS [
PMC10306223
Self-discrepancy induction
The self-discrepancy induction is a 50-item self-report questionnaire designed to induce a focus on self-discrepancies and elicit state-rumination [
PMC10306223
Visual Analogue Scales (VAS)
Three visual analogue scales were used: mood, experienced discrepancy, and focused discrepancy in line with previous research [
PMC10306223
Visual analogue mood scale
Participants were asked to rate their current level of sadness (0 –
PMC10306223
Visual analogue experienced self-discrepancy scale
Participants were asked to rate the extent to which they currently experience a discrepancy between their actual and ideal self (0 –
PMC10306223
Visual analogue self-discrepancy focus scale
Participants were asked to rate the extent to which their current thoughts were about wondering how large the difference is between their actual and ideal self (0 –
PMC10306223
Autobiographical Memory Test (AMT): Extended version
EVENT
The AMT [Participants were instructed to retrieve a specific, personal memory in response to the cue word by typing it into the available text box via Qualtrics within 60 seconds. In Excel, the text box was an enlarged cell. A specific memory was defined as a memory of an event which lasted less than a day and occurred...
PMC10306223
Experimental and control treatment interventions
anxiety
Groups were standardized in procedure and adherence was uncontrolled but monitored. Participants of both groups were encouraged to continue with any current medication or other treatment phase as they would have done otherwise. Both groups completed their respective daily practices at home, individually, for four weeks...
PMC10306223
Procedure
The study was administered online via Microsoft Teams and Qualtrics (Provo, UT). Participants attended an initial session during which they provided informed, written consent, demographic information, and were interviewed using the MINI-Plus for screening and diagnostic purposes. The first session lasted an average of ...
PMC10306223
Statistical analysis
MDD
JASP (0.13.1) was used for statistical analyses and an alpha level of 0.05 was used for all statistical tests. The study’s design was between-subjects (LKM, colouring). The participant characteristics (e.g. age, number of previous MDD episodes, etc.) and baseline scores on the mood measures (e.g. DASS, RRS, etc.) were ...
PMC10306223
Results
PMC10306223
Participants at baseline
The mean pre- and post-intervention scores for each group can be seen on
PMC10306223
Means and standard deviations for relevant variables at pre- and post-intervention.
depressed
Specific, positive (Pos-), and field memories include data regarding total mean numbers (across both remoteness conditions) while recent and remote specific include mean numbers from the free-recall condition. Mean proportions (prop) for specific, positive, and field data represent the mean number retrieved out of 20. ...
PMC10306223
Manipulation checks at baseline
No reliable conclusion could be drawn regarding a significant change in sadness following the self-discrepancy induction at baseline,
PMC10306223
Autobiographical Memory Test
The descriptive statistics for the AMT variables pre- and post-intervention are shown in
PMC10306223
Correlations between rumination and memory specificity at baseline
After inducing state rumination, a significant, positive correlation (Pearson correlation coefficient) was observed at baseline between trait rumination (RRS) and the number of specific memories,
PMC10306223
Autobiographical memory remoteness at baseline
To determine whether there was a tendency for more remote memories to be retrieved, we calculated the difference in number of recent-specific memories (up to one year old) versus remote-specific memories (over one year old) retrieved at baseline in the free-recall condition. Retrieval of recent-specific and remote-spec...
PMC10306223
Autobiographical memory valence at baseline
We calculated the difference in number of positive-specific recent memories (up to one year old) versus positive-specific remote memories (over one year old) retrieved at baseline in the free-recall condition. Contrary to expectations, no significant difference was revealed,
PMC10306223
Changes in negative affect, rumination, self-compassion, and self-discrepancies, from pre- to post-intervention
depression
Bayesian repeated measures ANOVAs were conducted on negative affect, rumination, self-discrepancies, and self-compassion with time (pre-and post-intervention) as a within-subjects factor, group (LKM, colouring) as a between-subjects factor, and intervention compliance as a covariate. An analysis of residuals confirmed ...
PMC10306223
Changes in memory specificity from pre- to post-intervention
A repeated measures ANOVA was conducted on the total number of specific memories on the AMT (across both remoteness conditions) with time (pre- and post-intervention) as a within-subjects factor, and group (LKM, colouring) as a between-subjects factor. An analysis of residuals confirmed the assumptions of linearity. Re...
PMC10306223
Changes in positive memory retrieval from pre- to post-intervention
positive-specific memories
A Bayesian repeated measures ANOVA was conducted on the total number of positive-specific memories (across both remoteness conditions) with time (pre-and post-intervention) as a within-subjects factor, and group (LKM, colouring) as a between-subjects factor. An analysis of residuals confirmed the assumptions of lineari...
PMC10306223
Means and standard deviations for memory valence and vantage perspective at pre- and post-intervention.
depression, positive-specific memories
Data include total mean numbers of specific memories (across both remoteness conditions).A Bayesian repeated measures ANOVA was then conducted on the number of positive-specific memories in the free-recall condition using remoteness (recent and remote) and time (pre- and post-intervention) as within-subjects factors, a...
PMC10306223